All right, we'll get started everyone. Good morning. My name is Jason Thompson, Head of Investor Relations for Indivior. Thanks for joining us today. We have a fulsome program for you and are excited to share it with you. Before we get started, just some housekeeping items. Allow me to remind you that our presentation includes forward-looking statements. Actual results may differ materially from those statements. We list some of those factors on slide three. Also, our presentation will use adjusted non-GAAP financial measures. We provide a reconciliation of the adjusted measure to the reported amounts in the appendix to the presentation. The presentation is available on our website at www.indivior.com. Moving to the agenda, which you see here, we've got about four hours of programming. We'll have lunch afterwards. With that brief introduction, I'll turn it over to our CEO, Mark Crossley. Mark. Thanks, Jason. Welcome to everyone present today and for those joining online. We have three key aims that we're really trying to cover today. The first is we're trying to introduce a broader cross-section of the management team from Indivior. The second is we're trying to really demonstrate a clear focus on a creation path, sharing more granular details that we have before the medium-term horizon. Lastly, after today's session, we expect you to come away fully understanding why we're so confident in the future of Indivior. For those less familiar with Indivior, we're the global leader in addiction treatment. It's a highly stigmatized disease with less than 20% of those that suffer from addiction actually getting treatment. While those statistics are impactful, it's the personal story of each patient, some of which have been captured in our last five annual reports, that drive us. We imagine a better future for each patient. One in which our treatments can help them transform their lives. Helping these patients is why so many stakeholders. Helping those patients who so many stakeholders have left behind is what drives the entire Indivior team. We'll also look to expand this patient focus both through the management presentations, but also through an interview with Dr. Terry Horton, our Head of Patient Insights and Advocacy, and Dr. Santoro, who's a national key opinion leader in the treatment of addiction, who's been practicing for 30 years. A real patient focus today in addition to the financial story. From the individual patients back to the statistics, which are staggering, and there's a huge task ahead to help patients and eliminate the stigma of addiction. It's a growing global crisis, whether alcohol use, opioids, cannabis, or stimulants and cocaine. Over 300 million people use opioids, cannabis, and stimulants. Alcohol, which is the largest, most normalized disease within addiction, has billions of consumers and 108 million people globally suffering from alcohol use disorder. Addiction is a chronic relapsing disorder of the brain, medication-assisted treatment is a critical part of the solution to the global crisis when combined with counseling and behavioral therapy. In the U.S., our largest market, the number of people dying from overdoses rose dramatically during the COVID pandemic and is still near all-time highs. In 2021, over 200 people a day died from opioid overdoses. A truly shocking statistic, 89% of those involved a highly potent synthetic opioid such as fentanyl. The need has never been greater as the opioid crisis is one of the largest and most urgent public health emergencies of our time. Against this backdrop, Indivior's purpose, vision, and mission could never be clearer or more pressing. Our purpose is to pioneer life-transforming treatments. Our vision is that millions of people across the globe suffering from substance use disorders and serious mental illnesses have access to evidence-based treatments to change lives. We take our role as stewards of these medications extremely seriously. Under our guiding principles, we cultivate a unique patient-focused culture, which has a foundation of integrity and compliance and entrepreneurship. For those less familiar with Indivior, we are the global leaders in addiction. We have over 900 team members across 39 countries, all encouraging patients to have access to evidence-based treatment to change their lives. In the most recent 12-month period, we had $882 million of revenue, of which 80% came from the U.S. In that time, SUBLOCADE, our transformative asset for opioid use disorder, has become our largest selling product. We're primarily focused in the U.S. market, you can see we have 20% of our business outside the U.S., which remains a valuable source of diversification as well as profitability. Last but not least, we're well capitalized with over $1 billion in cash and investments on the balance sheet, which gives us tremendous strategic flexibility, especially in such challenging geopolitical and economic times as we're experiencing today. Our senior management team, many of whom you'll hear from today, have deep pharma and disease space expertise. We've got an extremely strong board with a strong value creation record and five new members refreshed since 2021. I'm incredibly proud of the talent and the caliber of both our senior leadership team and our board. Combined, we have the right skills and experiences to execute our strategy and deliver sustainable shareholder value creation. This slide sets out our strategic priorities, which we expect to drive this substantial shareholder value. First and foremost, we plan to grow net revenue of SUBLOCADE to more than one and a half billion dollars. This represents an uplift on our previous target of greater than $1 billion. We seek to diversify our revenue both organically and through business development while maintaining our focus on the treatment of addiction and comorbidities. We will build and progress a comprehensive pipeline to address the key addiction disorders and augment our global leadership position. We'll optimize our operating model to deliver scalable growth and strong cash flow for reinvestment in the business and potential returns to shareholders. These strategic priorities have been in place since 2020, and the alignment and execution against them has driven our success. Since 2020, we have grown net revenue by approximately 40%, driven primarily by SUBLOCADE and the relative stability of our legacy film products, which I'll remind you, we do not promote. Over the medium term, we expect to deliver an attractive double-digit compounded rate of annual growth in net revenue. You should note that this is before any potential net revenue benefits from our proposed acquisition of Opiant, as the deal has not yet closed. Ryan will take you through the building blocks a bit later, but the growth profile will be primarily driven by SUBLOCADE, which we expect to exceed a billion-dollar run rate by the end of 2025, progressing toward our new peak net revenue target of greater than $1.5 billion. Additionally, we expect meaningful growth contribution from PERSERIS, our long-acting schizophrenia product. We remain confident and committed in the view that PERSERIS has potential to deliver net revenue of $200 million-$300 million, and you'll hear more about that today. Our plans also envision a return to growth in the rest of world, led by new product introductions such as SUBLOCADE and SUBOXONE film. Lastly, we continue to expect film share in the U.S. to revert, excuse me, to historic industry analogs. We expect the growth in net revenue to transfer to compelling medium-term profitable growth and strong cash flow. The scalability of our business model means we expect to deliver positive operating leverage. Again, Ryan will take you through the building blocks a bit later, but we see scope for significant margin expansion over the medium term, even though we plan to increase our R&D expenses towards industry benchmarks as we build a deeper, broader pipeline. Lastly, we expect the combination of strong net revenue growth and operating leverage to drive strong cash flow, which we will deploy according to our capital allocation strategy. We have clear capital allocation priorities. These are focused on, one, reinvesting behind our growth drivers and our pipeline. Two, maintaining flexibility and meeting our obligations. Three, diversifying the business. Four, returning excess cash to shareholders. Our robust balance sheet and prospects for strength and cash flow mean we're well-positioned to assess inorganic opportunities for investing and diversifying our business. As I touched on earlier, any opportunities would have to potentially strengthen our leadership position in addition to creating shareholder value. Last month, we saw a compelling opportunity which met these criteria in Opiant Pharmaceuticals, which we have signed a definitive agreement to acquire for $145 million upfront plus contingent value rights. While we can't go into greater detail in the presentation as the acquisition hasn't closed, let me summarize briefly why we strongly believe the addition of Opiant to Indivior is both strategically and financially compelling. It will strengthen our leadership position in addiction and science across the continuum of care, including treatment and rescue medications. In particular, through the addition of Opiant OPNT003. If approved, we believe this would represent a highly relevant, fast-acting, long-lasting rescue treatment for fentanyl overdose. It would provide a near-term and relatively de-risked growth opportunity. We believe Opiant OPNT003 has the potential to reach peak net revenue of $150 million-$250 million. With an attractive margin profile, we believe it'll be accretive after the second year of launch of OPNT003. Third, we also believe that bringing aboard the Opiant team would further bolster both our commercial and scientific capabilities. Expanding on the rationale, this slide, it sets out our unrivaled addiction treatment and science platform across the continuum of care that would be created by combining Indivior and Opiant. The combined portfolio of marketed and investigational targets would have potential to address some of the most urgent and growing needs in addiction, including opioid use disorder, alcohol use disorder, and cannabis use disorder. This portfolio would be supported by complementary addiction-focused commercial capabilities. In Indivior's case, accessing organized health systems, including regional hospital centers, government healthcare systems, and justice systems, while in Opiant's case, their expertise in the public sector, chiefly law enforcement and first responders. Lastly, we'd be bringing together powerful addiction science, development and advocacy capabilities, while including delivery mechanisms expertise from LAIs and orals from Indivior and nasal delivery technology from Opiant. We'll have more to say about the acquisition, which we expect to close in 2023. However, I remind you, it's subject to approval by Opiant shareholders as well as customary closing conditions. Now, let's go to the very important topic of sustainability. At Indivior, we strongly believe our long-term success is directly linked to operating in a responsible way and in a way that minimizes our impact on the environment. Admittedly, we're early in our ESG journey, yet we're integrating it into how we operate the business every day. Our ESG strategy operates under five main pillars. These encompass our approach to patients, our people, business integrity and compliance, the environment, as well as the supply of our medicines to patients. We're signatory and operate under leading sustainability reporting frameworks. These include the Task Force on Climate-related Financial Disclosures, the Sustainable Development Goals, the Global Reporting Initiative, and the UN Global Compact. The importance to Indivior of operating responsibly was further recognized by the appointment of Nina DeLorenzo to the role of Global Impact Officer, and you'll hear that from Nina a bit later in the presentation. Lastly, let me finish our objectives for this event. By the close of the meeting, we hope you'll be given a deeper understanding and insights into the key themes. Indivior is the global leader in addiction, and we are at the forefront of combining deep patient and disease state insights with breakthrough science. Sublocade is a transformational asset for opioid use disorder, with net revenues expected to be in excess of a billion and a half dollars. We're pursuing diversification opportunities in addiction and its comorbidities, both organically and through business development. Lastly, we will maintain our focus on operational excellence and expect to generate significant free cash flow in the coming years to support our strategic priorities. With that, it's my pleasure to hand over to my colleagues to take you through the journey in more detail. This is a strong team. I'm extremely proud of their commitment and dedication to our purpose, vision, and mission. I'd like to introduce now Richard Simkin, our Chief Commercial and Strategy Officer, who'll begin the deep dive on our transformative treatment and number one priority, SUBLOCADE. Richard. Thank you, Mark, and good morning, everybody. Today I'm gonna be taking you through more details on SUBLOCADE and how we see the unlocking of the greater than $1.5 billion net revenue opportunity that Mark spoke about briefly just now. I'll be helped and joined by Vishal Kalia. He's our Vice President for US Commercial Access, and I'll also be joined by Dr. Terry Horton, who is our Patient Insights and Advocacy key representative. This morning, what I was gonna do is go through five areas. First of all, we'll take a look at the global footprint, and we'll see where we are today and how we view the market. We'll then take a look at the opioid use disorder market. I'll share with you some of the insights that we see, some of the things that we think are encouraging and why we should think about them in a certain way. I will hand to Vishal, who will go through the four areas that we think will be critical to continue to accelerate and drive to the greater than $1.5 billion. We'll then look at the SUBLOCADE potential, we'll close this section out with a Q&A. I think you'll find that incredibly insightful. This is with a practicing healthcare professional, Dr. Santoro. I think he's really gonna bring to life for you what life is like dealing with patients in this area, the challenges, the good, and how our products really help and fit with this. First of all, Mark Crossley spoke, and today we're going to concentrate a lot more about the U.S. market. Before we do that, I want to talk a little bit about our global footprint. Today, we operate in about 39 countries. We have clearly an important U.S. business, which we'll talk about, but we also have a rest-of-world business. As you remember, it represents about 20% of our net revenue. It's a profitable business, but it's a business that's relied upon heritage products for a number of years. On the right-hand side, you can see there SUBUTEX PR or SUBLOCADE or SUBOXONE film. We now have SUBOXONE film registered in about 36 countries. While that may be old news for the U.S., it's not old news for the rest of world, and we believe this will be a great opportunity for patients and healthcare professionals to have a real choice for their treatment. We're also now registered in 12 countries for SUBLOCADE. Again, we're excited to roll that out into our rest of world geographies. We think, again, having that offering will be something really good. This is the confidence we have with regard to, you know, returning the rest of world business back to growth. We spoke about the U.S. Why do we see the U.S. as by far the greatest opportunity? Well, first of all, it starts with, you know, what's happening. If you look at prevalence of misuse of opioids, the North America region, it's the greatest area of issue per capita of prevalence. If you consider the millions of people within the U.S., you can quite clearly see that becomes by far and away the largest issue that we can address. If you look at the market dynamics, you'll see there what's been happening is we've had liberal prescribing of opioids. This market is about an opioid market where people have been getting prescriptions. I'm gonna talk a little bit about what's happening to patients and why. Yet we have a significant treatment gap, so only one in five people are actually getting treatment in this area. That represents a huge opportunity. Again, we'll touch a little bit on some of the barriers, some of the things that we think we can remove. The U.S. is very clearly a recovery model, what that means is that we want to get people into treatment, we want them to recover their life. What we mean by their life is back in employment, back with a loving family, all the things that we may take for granted. Then finally, the other issue that we see is very much a limited patient access still to treatment, and I'm gonna talk about those numbers now. Let's just look at how many people we're talking about within the U.S. Now, there are many, many different ways you can look at this with different sources. What they all say is there is a significant number of people who are misusing opioids, and it ranges from anywhere between 9-12. We take the middle area, we're around about $10 million is what we believe is a good number to look at that. If you look at people who are diagnosed, so that's a DSM-V criteria diagnosis, that's approximately about $3 million. If you look at those that are receiving treatment, within a year, only about $1.8 million people are receiving treatment. We have this huge gap and opportunity to close that treatment gap, that's a real issue that we're seeing in the U.S. Why is that? Well, before I go to that slide, let's just talk a little bit about. One second. That's okay. First of all, I want to bring to life why it's such an issue in this marketplace. Mark already shared this slide, and you can see what's happening here with the ever-increasing concerning trend of opioid overdose. What's happening is that fentanyl is really the underlying issue that's happening in this marketplace. Now, just to understand fentanyl a little better, the challenge with fentanyl is that it's synthetic. That means it's man-made, it's cheap to produce, and it is highly potent. It is not like heroin. It's significantly more potent than heroin, and it's polluting the illicit drug market. What that means is you may believe you're taking something, but actually you're taking something that's laced with fentanyl. That could be cannabis, that could be cocaine, that could be another opioid. The challenge that we have here is that if you relapse, that is a way greater issue than maybe what it might have been in the past because you're really putting yourself at way greater risk. If we now think about the patient and the patient journey, you know, on the right-hand side there, we've got our annual report, and each of those capture the patient and their journey. What you'll realize with these patients is a lot of the themes are very similar. There's a reason they became hooked, an addict, whatever language you want to use, but suffering with opioid use disorder. A lot of those reasons are, may not be what you realize, they're to do with overprescribing. An accident, you go to your physician, you start getting a prescription, and before you realize it, you've actually got yourself into an opioid issue where you're needing that drug more and more. From there, it then starts to fail. Some people, for example, Kyle, on the top right-hand side there, he's suffered for about 10 years. In and out of treatment, recovery, relapse, recovery, relapse, lost a job, lost his flat, had to move back in with his parents. This is really challenging. Who would have known? This started with a car accident, and he got prescribed hydromorphone. From there, that led to 10 years of a really, really challenging situation. The good news for Kyle, he's now in recovery for the last 3 years, and he's doing incredibly well. Along his journey, he's dealing with things like stigma. When he was trying to get reemployed while he's in recovery because he has an issue with the legal justice system, you know, that was really hampering his ability to get back into work. You're dealing with lots of things. The really key important point is, we look at the treatment gap, 10 million, 1.8 million being treated. You consider the risks that we are now seeing in the marketplace that you may inadvertently use fentanyl and the highly likelihood that if you do, you could seriously overdose. That really drives us as an organization. Let's look at what's happening in terms of treatment capacity in these areas. Now this graph on the left-hand side, in some ways is very good. You'll see a significant increase in ability for doctors or healthcare professionals to be able to treat in this area. To treat in this area, you have to be waivered, and that means that you're able then to prescribe buprenorphine or a drug like ours. What you see here is a significant increase, and this has been driven by relaxing of laws to do with nurse prescribers, physician's assistants being able to prescribe. More recently, what we're seeing is now, HCP can prescribe up to 30 patients without a waiver. Those trends are great, but still today, only 120,000 are actually able to prescribe. If we move to the right-hand side, this is even more concerning because this is saying of the 120,000, how many are actually prescribing? Today, only 48,000 are actively prescribing in this area. You think about the 10 million and the ability, even if you want to do something to find a healthcare professional that's able to help, you've got to only find something like 48,000 that are actively prescribing. That's truly a concern for us. One of the questions we get asked is, "Well, why are people getting waivers and not prescribing?" There are multiple reasons. It may be that they wanted to help one patient. It may be that their practice wanted them to have a waiver, but they're not actually prescribing. There are many reasons. The concerning issue is that only 48,000 are actively prescribing today. However, if we look at where the landscape is, we actually believe it's incredibly favorable for the future. Actually we feel very positive about this. I think it starts at the top. If you look at the State of the Union Address this year, in March, President Biden came out with four core areas. One of those right at the heart was stop opioid addiction. Right at the heart, starting at the top, and as you know, then that triggers all the departments looking at ways to help and what can we do. We even see areas like criminal justice system, and we're gonna talk about the importance of criminal justice system later on, and Vishal will cover that. What we're seeing even there is we're getting guidance not just from the president's office, but from the DOJ, talking about the need and why you should be treating the population who are suffering with opioid abuse addiction. The statistics are staggering when you look at that. The chances of relapse, the chance of overdose are much greater when you come out of a criminal justice system. Again, really at the heart of what we want to do is really tackling that area. We looked at expansion, and we talked about the physicians and how many are waivered. If you look at what's happening there are a number of things that potentially will help to relieve and normalize and destigmatize this area. At the moment, one of the things that I'm excited about is there is consideration to remove the DATA-Waiver removal. What that would do is it would mean it would make it more like a normal medication. You could visit any physician or healthcare professional, and they could prescribe it. Again, normalizing, destigmatizing. The 120,000, that would disappear because potentially everyone's able to prescribe. There are other areas, things like Medicaid Reentry. What is Medicaid Reentry Act that you might have heard about? Today, people within the prison system, the jail system, when they leave, even if they've been getting treatment, they don't have insurance coverage, and it can take anywhere between 30, 60, 90 days to reengage with that. What we think is important is that, you know, they should be allowed to reengage before they leave so that when they come out of the system, they can continue with their treatment. Again, as we know, this is a challenging area. Relapse is real. Relapse is scary, so we want patients to continue with their treatment. Again, that's something that's happening. Telehealth. This was something brought in during the COVID times. At the moment, again, telehealth is important. Patients can reach out, can get prescribed, are able to be dispensed, and that continues to be something debated with regard to extending and continuing in this area. The other important area is funding. Year-over-year, we're seeing increased fundings. This year it's about GBP 6.6 billion, which was half a billion up on the prior year. Importantly, if you look at the recent opioid settlements, these are in the tens of billions of dollars. Over the next 19 years, once all parties agree, they're gonna be flowing down into communities, into states, and these are meant and going towards the treatment and the of opioid use disorder. Significant increased funds that will make a big difference at the state level with regard to treatment and closing that treatment gap. Bipartisan alignment. What we're seeing is that this is one issue where both sides are actually pretty aligned on one, tackling this crisis and going about it in a good way, looking at all avenues of how we can close the treatment gap. We have bipartisan alignment, and why that's important is that when we have bills or policies, we have a greater likelihood that hopefully they will be passed and go through and actually make it down into the areas where it will make a difference. We see from there many policies that are now starting to flow through, and we spoke about two or three of them previously that we think will make a difference. Just to come back before we pass to Vishal. We're expecting significant market growth. We've been seeing mid to high single digits. We expect that will continue. When you look at the environment, when you look at the favorable landscape, when you look at the treatment gap, there is no reason to believe that this will not continue. Next one is the increased access to treatment. You've seen already that the increased access to treatment has continued for many years. We see that path getting steeper. The number of active physicians continues to grow, and we believe that that trend will also continue to go. On top of that, potentially there are areas where access will be eased even further. We have a favorable political landscape, which is going to help ease some of the areas that actually make it hard today for access, or it stigmatizes this disease space. We believe that by about 2030, the number of patients in treatment will increase from about the 1.8 that we shared with you earlier on to around about 2.8 million. Again, very favorable sort of like dynamics in a market where we have a real opportunity to close a significant treatment gap today. With that, I'd like to hand over to Vishal. Vishal is going to take you through really more detail of the areas of the accelerators that we believe are important to deliver greater than $1.5 billion. Bye. Thank you, Richard. A very good morning, everybody. I will take you through a deep dive into the four accelerators of SUBLOCADE growth that will enable us to deliver potential net revenue in excess of one and a half billion dollars. Oops. Go again. There we go. We have delivered nine quarters of sequential growth, and the latest quarter in excess of $100 million. The momentum continues to build, as you can see. It is a delightful position to be in when the score strategy is already been validated in the market over a longer period of time. This with a real market delivery, and this further increases our confidence in our strategy. My first core message today really is our strategy remains consistent. The four key accelerators to continue on the growth trajectory. That has enabled the growth thus far. I'll talk you through each four of them. The first one, the bedrock of our strategy, which is the unique product built on a transformative science. Number two, further accelerate the adoption in the organized health systems that has been proven to drive majority of the growth thus far. Expand access in the criminal justice system, an opportunity to help an underserved patient population with a deployment of a truly integrated plan. Last is based on the in-market learnings, a tailored infrastructure enabling both the patients and the providers. It all starts with the product. SUBLOCADE is a paradigm shift for patients, for providers, and infrastructure. Genesis of SUBLOCADE really is based on science and our intimate understanding of the patient base, which translates into a belief that patients don't fail treatment fails patient. Looking at the features of SUBLOCADE, which is developed and designed to deliver greater than 2 nanograms per ml therapeutic dose over the entire dosing period, resulting in a greater than 70% opioid receptor occupancy. It is the only product uniquely designed to deliver greater than two nanograms per ml over the entire dosing period. Maintaining higher and sustained levels of this therapeutic concentration is important, particularly in face of the fentanyl crisis that Richard referred to earlier on. From a patient's perspective, it is consistent. There are no ups and downs. There is no supplemental doses required in any of the treatment settings. Where patients make one decision once a month rather than 30 decisions, and that across a year is 12 decisions versus 365 decisions. We know patients struggle is very real. This is a disease that is relapsing in nature. We know on occasions patients can slip, and they can go back into the old habits. With Sublocade on board, at therapeutic level, they do not feel the rewarding aspects of it. What does it mean in simple English? It means you don't feel the high, the very reason that you take opiates for. This product attribute also translates and echoes in the patient quotes that I will share with you all. What they say about SUBLOCADE, which has the potential to help reshape their lives. I will read out some of the key highlights where they speak about, "It helps me back to the mindset of a normal person. It gives me the peace of mind, less to worry. I don't wake up in the morning saying, 'Where is my medication?' With the help of the medication, I can live." In simplest of terms, that means that it gives them normality as they go through their recovery journey. We're also building a robust real-world evidence database, which Christian will come and share in greater depth of detail across conferences, real-world publication with 200 plus in progress, which Christian will share in a greater detail shortly. Moving on to the second growth accelerator for SUBLOCADE, which is organized health systems. As Richard alluded to earlier on, there are 10 million patients who abuse opioids. 3 million diagnosed. If I break down roughly the 3 million diagnosed patients, what you will see is majority, circa of 80%, sit in the organized health system space. It is a growing area where we are well-positioned today and for the future. Let me break this down for you and look at individual components of that side of the slide, which is the organized health systems. When I talk about integrated delivery networks, we speak about the likes of American Health and Hospital, like the Kaiser Permanente. These are bigger systems, bigger treatment settings. When we speak about the federal health systems, we speak about the likes of the Veterans Affairs, the Indian Health Service, the DoD. When we speak about key accounts, we speak about Savitr Health comes to mind, Second Chance Treatment. Lastly, the criminal justice system, where we talk about both incarcerated patient population and also patients who are released for, in community or on parole or probation. As you will see, the total on of the organized health system equates to greater than GBP 3 million, and that's because the patient population is transient. They move from setting to setting, and that's what you would see from that. What I have done for this exercise today and the presentation to bring to life some of the unique dynamics is break out the organized health systems and the criminal justice system separately to bring to life the unique dynamics that each of them have. To bring this to life, the strategy to life, we developed a very unique ecosystem model. As you can see on the graphic on the far side, we spoke about how patients are transient. Just to give you an example, you can have a patient in a residential treatment center or in a criminal justice system, and they can go out in the community, go to an IDN, go to a local physician, go to a practitioner in the local setting. Same for physicians, that physicians are also transient, and they do cover a number of the systems. You may have a criminal justice system outsourcing their medical needs to people and providers out in the community. Not only that, this ecosystem is uniquely supported by a number of variables like the policy, like the local access requirements, like the rules and regulations and the treatment community, amongst a number of variables. What we did when we designed our ecosystem is we took a number of variables into factor and designed that for ecosystems. Particularly, it's also important to know for SUBLOCADE that with SUBLOCADE, the market is also transitioning from retail to specialty. It's important, the bedrock which is ensuring the access pathways are created across all the systems as we move forward. As we transition from retailing to specialty. To support this shift from to the OHS strategy, we redesigned our go-to-market in fall of 2020 and redeployed and invested significant investments in the ecosystem with a team now greater than 350 people who are incredibly passionate and committed to serving the cause of patients. This model is a scalable model where we have the expertise built in as we scale and take the business forward. Over the last two years, you've heard from Mark and Ryan talking about the access in the organized health systems at a parent level, which was 500 parent who were based on different variables. We prioritize them across the nation. That target has been met. That has been enabler of the growth thus far. What I will do today is aim to take a deeper dive underneath those 500 parents into three unique vectors. Number one, facilities. Let me bring that concept to life. A parent could have a number of facilities underneath them, ranging from a handful to some cases hundreds, and also with varying degree of decentralization. To put that in perspective, those 500 headquarter entities translate roughly between 10 to 16,000 facilities. Second, within those facilities, there are doctors who treat relevant patients. You've got to activate the facility, enable the pathways in line with the headquarter alignment, and then there are patients. When those two things happen, there is then patients available in those facilities, which is between 1 million - 1.5 million patients. As you can see, as you trickle down those five into 10 - 16,000, then the physicians and then the patients. In a directional sense, it kind of makes sense that you have access, you establish it, and then the treatment pathways open up.What I have also done is provide a further granular level of that information. As you can see from the concentric wheels, is based on the total potential that we see. The darker shades on the other side are based on the achieved thus far. I'll bring your attention to the broader shape of this, which is in the innermost circle, there is the OHS facilities. We are making good progress in that area. The one outside that is the number of physicians in those facilities, and the total universe is the one we see where there is potential and patients. We believe that those two are accelerating. We're creating access. Physicians are advocates enabling patients to grow as we move forward. Taking a deeper dive from that is my next slide, which looks at two examples. two examples of two organized health systems. Here you see a major national organized health system, and on the other side you see a major regional organized health systems. Whilst the shapes are broadly similar, but they also differ as you can see. On the other side, on the top, there's a major national. We are making inroads into activating the number of facilities, the HCPs and the patients. We are in the early stages of that with 100 facilities. On the other side, in the major regional, we're already halfway through in activating facilities. You can see the scope and where they are. That is also the reality of the field because each system is unique. They have their unique dynamics, but with our setup at an ecosystem level, there is variability to meet where our patients are and expand treatment. Because we understand the challenges, we can tailor our model accordingly at an ecosystem level. Moving to my third strategic accelerator, which is the criminal justice system, sorry. As the headline says, it is about turning the front door to opioid addiction into a step on the path to recovery for patients. Let me break that headline into two areas. First, the first one, which is the front door to opioid addiction. Why do we say that? We say that because greater than 60% of patients with substance use disorder pass through the criminal justice system. Sadly, they are 10 x more likely to overdose upon release to the community. Three-quarters relapse within the three months itself, and half are re-arrested within the first year. Those are quite sad statistics. Just take a step back and put ourselves in a shoe of this patient who is already prejudiced, stigmatized because of opiate use disorder, and then they have the burden of being involved in the criminal justice system. There really is a tough uphill battle. However, the tide is turning. There is an impetus to treatment expansion. As Richard alluded to few of the elements earlier on, we look at there is an increased legal activity requiring mandating that MAT is offered across the criminal justice system. A good example of that is New York, where the state has mandated that there is MAT available to patient population. Facilities. There is also $ being made available through the regular route but also through the grants, so that treatment treatments can be funded. We also believe that it is the right product with SUBLOCADE that is a good fit. As you can imagine, that criminal justice systems are not set up to be healthcare providers, but it has come upon them to expand access in all different areas. This is where with our integrated plan and all the right variables available, we can help them on paths with establishing access and moving forward. Why do we believe that SUBLOCADE is also a good fit amongst other treatment options? Let me bring an example to life. I have seen there on a number of occasions when visiting the justice system, administering an oral medication is a challenge. Let me bring a scenario to life where a healthcare provider, along with one or two, sometimes even more wardens, goes from cell to cell to administer a daily oral medication. They have to stand. They have to give them the product, wait there, depending on the protocol, 5minutes or 10 minutes to ensure the medication's been consumed, give them a drink, a Gatorade to see it's all good, and then you move. That's time-consuming. That's very lengthy. Imagine doing that in some of the bigger prisons where there are thousands of inmates with opioid use disorder. That can be challenging. We believe SUBLOCADE plays a very, very good time. In a way, timing is right because it's coming together of the right product, the impetus to expand the treatment paradigm, and we have a very humble aim in this area, that over the short to medium term, as we move forward, ensure and allow for access to be available to medication-assisted treatment in this area. Taking one layer deeper into the criminal justice system, it is complex and multifaceted. On top of not being the healthcare facilities. Let me bring a few elements to life for you. First one, when we think about the criminal justice system, what comes to mind are the jails. Federal jails, state prisons, county prisons where patients and inmates are behind the walls. That is true. There is also another element which has got more potential patients in the area, which is the area of parole, drug court, probation. There are potentially more patients in that area than there are behind the walls. There's a key challenge, which you can see in the second headline, which is transition of care is vital. It's vital on a number of touch points. What does transition of care means? Which is, as the name says, if you are behind the walls, you are on a medication, you're about to go back into the community. Amongst a host of factors, continuation of medication is a key one for the patient population. Recidivism is a big issue for almost a big proportion of criminal justice system, which is patients and inmates who are cycling in and out, in and out, which is not good from a societal standpoint, but it's not good from financial standpoint for the systems because these are expensive patients who need to be on treatment so they can be a valuable member of the society as they move forward. Decision-making is complex in the criminal justice system across all host of them. These are the challenges that we have also seen in lots of other areas, in larger systems and areas where we have the expertise and the clarity of strategy and plans as we move forward. To elevate the importance of the criminal justice system and to accelerate growth, earlier in the year, we deployed an integrated team dedicated to the criminal justice system, we are encouraged by the start that the team has made. In similar vein to the organized health systems, when I look at the same concentric circle for criminal justice system, I look at both the facilities and the patients because it's a captive audience. What we do believe there is a significant opportunity to expand access in the criminal justice system over a short to midterm because the base, they're new in the treatment paradigm. I think in the facilities, you can see there are between 8 fercilities-12,000 facilities where we believe there is potential as we move forward, and approximately 1.2 million patients in specific areas. We are encouraged by the progress we have made in this area with our not just our early glimpses of good delivery, but more importantly, when we've engaged over 1,000 entities. The feedback we get and the desire to seek help, seek education is there, which is very unlike a lot of areas. You know, my team always talks about it. It's like they feel very welcome because they need help. There is a need, and they don't have the relevant expertise in, in the right areas. We believe we made good progress, and this is a good start, and we'll review the results in it just as we all move forward. Moving to the fourth and a key accelerator, which is Based on our in-depth understanding, we have established a robust set of programs under the INSUPPORT umbrella to aid patients, providers, and the healthcare entities. We've broken this down for simplicity into three core areas, which is access to treatment, continuum of care, and acquisition process. Let me go in a bit more detail on all three of them. The first one, which is access to treatment, which is our managed care or payer coverage, which is the bedrock for patient access. We have very good high-quality coverage across the United States for SUBLOCADE, which we are very delighted, and team's done a phenomenal job there. Secondly, with our commercial copay assistance program, we have in excess of 90% of the needs of the patients are met, which is paying no more than GBP 0, which is a key enabler for the commercial-eligible patients. Moving to number two, which is the continuum of care. That has been also strengthened, learned as we've gone through the processes over the last couple of years. Let me bring a few elements. Richard mentioned there is a big cascade of funding being made available for different treatment settings, and that generally comes through, amongst other things, through grants. We have made available a tool which collates, as you can imagine, these are all very disparate sources, collects them in a central place to enable with an education mindset to see what's available so the right people can connect the 2 things together. Second, as simple as it may sound, find a SUBLOCADE treatment provider. It's vital. Vital for patients, for caregivers, for care coordinators. As you can imagine, if you are in a state and you're going out of state, you're in a residential treatment facility, you're about to go in a different state to find what is the treatment landscape in the area that I will live in. That is a key aspect. Linked to that is the transition of care specialists. We know this is important. Providers like Dr. Santoro. I remember my very first meeting with him, he said, "Treatment of transition of care is vital because the first question comes isSecond question generally when you're in behind the jail is what happens when the patients go out, and we have a big broad base of providers. Here are specialists who can look at what insurances you will have, what your benefit design is, who are the options of the providers, and that we make available through transitional care specialists. Lastly, in that equally important is the Community Reentry Program, CRP. As Richard referred to earlier on, that in some cases, amongst other things upon release. There are lots of things in their mind when they're about to be released and face the real world, in some cases after years of being inside those walls. Healthcare is one of not the top priorities for them, but is a priority of where would I get my medication because they don't have insurance for 30 days, 60 days. Through the Community Reentry Program, with eligible patients, we provide for an option for the medication continuity as you move forward. Lastly, through the acquisition process, as we have referred to earlier on, we are also transitioning from the market and the provider and the healthcare base from a retail setup, in essence, to a specialty. These are hub, and they play a vital role for providing relevant information, relevant services and education, both to patients and the healthcare facilities around insurance, verification, benefit design, around connecting them to a specialty pharmacy, triaging the cases amongst other benefits that they provide. Lastly is the channel distribution process to continue to provide access to the treatment as we move forward. That is the umbrella of INSUPPORT. In summary, as I talked you through the four core accelerators product, as I'm sure you can see, it is a paradigm shift based on underlying science and our intimate understanding of the patients. Organized health systems. It has been a proven growth driver. With the established ecosystem model, we are confident in continuing to provide access to patient and accelerate growth and the depth of adoption across facilities because we have the infrastructure, the know-how, the capacity with our compliance programs built into it. The criminal justice system is a clear opportunity to expand access to serve a really underserved patient population. Timing is right. The right coming together of the right product, the right opportunity, the right implement, the right program. Infrastructure. It's a strong infrastructure to enable patients and providers. All this combined together, we remain confident in enabling more and more patients on path to recovery, helping them to fulfill their life's unfulfilled potential. Moving to my last section, which is looking from a numbers standpoint. The strategy translated into a core KPI that we see, which is the patients. How do we help patients looking it through the patient's lens. We expect the organized health systems and the criminal justice system to account for a big growth, majority of the growth driver as we move forward. We expect in order to deliver a greater than $1.5 billion potential, we estimate we'd require about 12% share of the available patient opportunity in the organized health systems. In the criminal justice system, it's approximate 4% share of the available population part of patients in that area. To give you a flavor, also looking at the overall patient share, we estimate it'll be around 10% share in the year to realize the potential of SUBLOCADE, which equates to 270,000 patients. Bringing it all together, that the slide that you've seen on prior occasions is looking at the numbers starting from my left, which is 10 million misuse opiates in the United States. 3.1 million are diagnosed with OUD. To achieve SUBLOCADE potential to be greater than $1.5 billion, we estimate we need 270,000 patients. Underneath, from a market growth, we expect a sustained U.S. market growth between mid to high single digits, continue our access program and penetration in the organized health systems and the criminal justice system. Very importantly, the growing evidence base that Christian will come and speak about in greater depth and detail, where there are label updates, RECOVER study, fentanyl rapid induction, and a program of over 200 real world evidence conferences and publications. Thank you for your time. I will now pass you on to Dr. Terry Horton, who will take it from here. Thank you. It's my pleasure today to introduce Dr. William Santoro. Dr. Santoro is a family physician. He is board certified in addiction medicine actually since 1989, which makes him one of the first in the first group in the country to receive that honor. Dr. Santoro has treated patients with substance abuse and opioid use disorder since... well, for a number of decades, in east northeastern Pennsylvania, in the Reading area, in a number of different types of settings, your treatment program, private practice, in and in, lastly in a hospital system, Tower Health, where he's the sectional chief of addiction medicine, and has been seeing patients in the emergency room and on the floors. He takes care of all sorts of patients with substance use disorder, including a number from the criminal justice setting. Dr. Santoro is also a teacher. He is part of the teaching faculty of medical school, the Drexel University College of Medicine, where he teaches medical students, residents, and fellows in addiction medicine. He's currently the president of the American Society of Addiction Medicine's Pennsylvania chapter. So welcome, Dr. Santoro. Thank you, Terry. You heard a lot about criminal justice. You saw Michelle's, you know, talk where lots of information around criminal justice involved individuals, criminal justice system being a kind of a critical driver for the opioid epidemic. I was wondering if you could talk about the compelling need in that vulnerable population. The compelling need starts with the fact that there are, as Michelle had mentioned, there are over 3 million people in the United States who are diagnosed with opioid use disorder. Remember that between 80 and 100,000 people die of an overdose each year in the United States. When you look at the fact that the majority of inmates in our criminal justice system have an opioid use disorder or at least a substance use disorder, and yet only a small fraction of that actually receive treatment while there. That means that upon release, these people have a very low tolerance to their drug of choice, which makes it a very high risk for relapse and even a higher risk for overdose. I neglected to say I really should, to backtrack one second to say that you're here your own experience. You're being reimbursed by Indivior and any other disclosures you can find in the addendum. Regarding to treating patients with opiate use disorder from the criminal justice system, can you talk a little bit about some of the settings or setting opportunities that you've had to treat that population? First of all, to treat a patient through the criminal justice system, there are generally two tracks, and Vishal had kind of hinted at that. The two ways that occur is one, you can be hired by the criminal justice system to go in and have your office in the jail or the prison. That's not the way I treat that I come across my patients. The second way, which is more the way I do it, is that these patients, as they get released, now in my case, before they get released, I'm contacted by the criminal justice system, and they get referred over to me. This started really for me in about 2007, when I actually had a patient who was stable on medication. By the way, I don't use the term medication-assisted treatment. I use pharmacological treatment. There's nothing assisted about it. If you had diabetes, you wouldn't be on insulin-assisted treatment. You'd be on insulin treatment. I look at this as not an assisted treatment, but as a pharmacological treatment. Anyway, I had a patient who was stable on his pharmacological medication and was arrested for a back charge. When he went into the prison, they elected to stop his stabilized medication, something that would never be done in any other disease. They stopped his medication. Worse than that, they treated him with an opiate. You primed the pump. With my description of diabetes, it'd be the equivalent of not only taking the person off their medication but then feeding them ice cream. You're priming the pump for a disaster to occur. We went to the judge, who went to the warden, we started to talk about how do we treat this better. The problem back before 2007 was that what we basically had was non-medical treatment, AA, NA, which is perfectly fine. The next step up was methadone maintenance. That was a bridge too far. To go from non-medical all the way up to the highly restrictive treatment of methadone was just too far to jump. Buprenorphine came into play and has moved up as part of the standard of care, that has made the incremental steps a lot more doable. Mm-hmm. Can you speak about some of the challenges and barriers to care that you've seen over the number of years? Well, the biggest barrier, again, it was mentioned earlier, I guess I'm just putting it more into layman's terms. The biggest barrier to the treatment really has been stigma. Stigma harms. When you stigmatize a patient, they don't go for treatment. If they don't go for treatment, they don't get treatment. If they don't get treatment in this population, they're gonna go back to what they were doing before. It's a revolving door. They come out of a criminal justice system, they're not treated. If they stay alive and don't overdose and die, they end up back into the same situation, then from there, come right back into treatment again. I understand that you've had a lot of opportunity over the years to interact with some of the leadership in the criminal justice system, wardens in the prison officers, guards, physicians. Can you speak about that experience? Yeah. In my local community, I've been through three wardens. The original warden, we sat down, and we started to build a system. I'm not gonna tell you we didn't get pushback. In fact, I'll tell you just the reverse. We got a lot of pushback. To the point that I met with the medical staff of the local jail, one provider absolutely refused, flat out refused to treat these patients with medication. We had a bit of lawyers would call it a discussion, everybody else would call it an argument. We had a discussion about how this was supposed to happen and why it should happen. She said to me that she would give medication, but not to a person who tested positive for cocaine. When I asked why, she said, "Because cocaine is illegal." I said, "Well, then have the person arrested." I said, "You wouldn't stop their insulin just because they used cocaine. If you want the person arrested, report them to the D.A. and see if he wants to press charges. You should treat them medically anyway." She ended up resigning, which I respect. If you don't wanna agree and don't do it, then get out of the way and let the rest of us do it. Since then, we've built the program, and I'm proud to say that I feel like I'm part of moving the needle on the standard of care and the evolution of the standard of care for these patients. Can you speak a little bit more about that evolution? You know, when I first started back in 2007, nobody asked a patient if they had a problem. It's human nature. You don't wanna find out a problem that you can't take care of. Why discover something that you then have to toss your hands up and say, "I can't help you." Nobody would ask. Today, it's one of the first questions that's asked when an inmate, I call them patients, they call them inmates. When an inmate shows up in the criminal justice system, one of the first questions they ask is, "Are you using illicit drugs?" Second question: "Are you gonna go into withdrawal?" Third question is: "Do you want help?" Those questions were never asked before because they didn't have any way to deal with it afterwards. We've seen it to the point that, you know, leadership starts at the top. I know that sounds obvious, but it really does. It starts at the top. Things change from the top down. Once the warden, once the doctors, the providers start saying, "Yes, we're gonna treat this," then it trickled down from there to all the way down to the corrections officers. In fact, Terry, I was telling you about just yesterday, I had seen a patient in the hospital, and I knew he was part of the criminal justice system because he was in shackles, and there were two guards with him. I explained to the patient that we were gonna start him on buprenorphine, and he questioned appropriately and said, "What about precipitated withdrawal?" A medical condition that if you start too soon. I said to him, "You know about precipitated withdrawal. You know if my giving you this medicine at this time is gonna cause harm. What I want you to do is to tell the nurses and the doctors if you're not really ready to get this medication and refuse it." I said, "They might give you some trouble." At which point, the corrections officer jumped in and said, "Don't worry, Doc, I'll take care of him." That has never happened before for a corrections officer to be on the patient's side and say, "I'm gonna help you to make sure that that doesn't happen. It's a remarkable change. Based on your own experience, with patients tailoring treatments to their needs and the evidence that's available to you, can you describe your role, like, how you consider the role of long-acting injectable buprenorphine? Yeah. I started using Sublocade. I'm just gonna call it SUBLOCADE. It's the only product out there today. I started using SUBLOCADE the day it came out. It was difficult at first. You know, whenever a new product comes to market, this is just typical, this isn't individualized to SUBLOCADE. The insurance companies immediately said, no. It's a knee-jerk reaction. It's a new medication, they're gonna decline it. The process has gotten easier and now most of the insurances do cover it one way or another, or we get it done. The beauty of it is that, you know, when these people come out of the criminal justice system, as it was alluded to earlier, they don't go right home. There's usually a stopover, they go to a place like a sober living house. Sober living houses are very regulated. Everybody, you know, you have to have a community meeting of where they're gonna be put up, and you have to have approval. The whole community knows that on that corner is a sober living house. Along with the community knowing, so do the drug dealers. When a patient is now sent to a sober living home and they walk out, who do they encounter? All the drug dealers who are ready to entice them to get back into their way of life. Having an injection, you know, they come in, they're gonna say, "I'll buy your medicine. I'll swap you your medicine for some heroin." I got some good stuff today, so I'll swap you with it. You can't do that with an injection. They've made the decision to get the injection, and they're done. There's no pressure. They can't be pressured to change it. I'm sorry, Joe dealer, I can't give you the medicine if I wanted to. It was injected in me, so we're done. That has been a major change. You know, the troubles with that these people are going through, those us in this room will never experience and never even think of. We all got here today. I took a subway, somebody probably drove in, somebody took a cab. Never thought about it, did you? You just did it. These people, transportation, something as simple as transportation can be a major barrier to care. How do I get to work? How am I gonna get from here to my treatment provider? When they get discharged from the sober living home, how am I gonna go from where I was to my new home, which is two counties away, and how am I gonna get my treatment? I don't have the access to care. I don't have the transportation. These are things that you and I never have to worry about. These logistics of transitioning from behind the walls in supervised settings out into the community to continue your recovery journey. How is you or your office have they been able to interact? Are there are these logistics starting to be solved? The thing that I tell my patients and when I go and give lectures is that anybody who thinks that you're gonna treat these patients with just the medication, they're gonna fail. That's not gonna work. You need a whole program, which is, you know, again, what some others had intimated at because they talk about INSUPPORT. This is more than just medication. If you just give the patient the medication and nothing else, when the medicine stops, and ultimately it will stop, they have nothing else to rely on. They haven't built anything. What we've done, we have case managers. We set up programs for them to go to counseling, to get to psychiatric needs. They need their mental health taken care of. They need a place to live. They need a roof over their head. If you're gonna tell a patient, "Listen, you got to get your medicine and you got to go to counseling," and they don't have a place to sleep tonight, that's gonna everything else is gonna be put on the second shift. The number one priority becomes, "How am I gonna get through tonight?" Not, "How am I gonna get my medication?" We've got all these other things that we take care of. Case managers within the office, nurse practitioners, LPNs, RNs, all pulling together to get these social determinants taken care of. On behalf of Indivior, Dr. Santoro, I want to thank you for coming in this morning and sharing these insights that you've garnered over a number of years taking care of folks with opioid use disorder. A couple key points that kind of really resonated for me and in my practice is really that these groups of patients, particularly the criminal justice involved, really are kind of the epicenter of a lot of the epidemic and kind of driving it with their recidivism, with their risk for fatal overdose. Yet there are emerging strategies that are happening both inside the prison and out to identify those individuals, engage them, have them started on treatment, and then transition them into care in the community. One thing really, I think a really burning issue that or burning topic that kind of comes to the light for me is that, there's an evolution, and there's been an evolution in this setting, in part with doctors like yourself, working together with criminal justice leadership who are changing and helping now. I think that's really, I think, a critical component that hasn't been there in the past. Thank you again for coming in and sharing with us. You're welcome. First of all, I'd just like to say a big thank you to Dr. Santoro. I hope you found it illuminating. I certainly did. Every time I speak to a frontline healthcare professional, I learn something new. I think what's great is you get the challenging nature of this disease and what we've done to build a great infrastructure to really make it fit with the needs of the patient and the needs of the healthcare professional. Before we move to Q&A, first of all, what I wanted to do is just really summarize, hopefully, what you've heard today. One, we really believe there's a path to achieve greater than one-and-a-half billion dollars opportunity. That's built on three core areas. First of all, market dynamics. We believe that the funnel expansion will continue. I talk about the funnel expansion, it's taking the 1.8 million people that are in treatment today and moving them more and more closely up towards the 10 million that really could do with need of this area. We're seeing great legislative momentum. Again, we're seeing errors easing and treatment access being really focused on to try and help with this opioid epidemic crisis. We're seeing funding increase two ways, the standard funding delivery. Secondly, the opioid crisis dollars that will be paid out over the next 19 years. Our product, as Vishal talked about, really at the heart of what we're doing. Our product is transformational. It's the only product unique that delivers greater than 2 nanograms per ml for the entire dosing period. That means if the product's on board, you're in good shape for that month. There's no ups and downs, and there's no other considerations about when I need to take my product. I think again, Dr. Santoro really brought that to life for you, the need and the importance of getting that product on board. When you consider what's happening with fentanyl and the risk of relapse, ever more important that you have a product on board. Finally, Vishal again, really went into great detail with regards to our building blocks. You know, we're driving growth from the organized health systems. We believe we've got a very unique go-to-market model that's allowing us to drive more and more penetration in that area. We started this year with a new team in the criminal justice system, and we're very pleased with what we're seeing. We're having a lot of interest coming inwards. As Vishal spoke about, you know, we're welcomed in these areas. They don't know what to do. They don't know how to start. There's a lack of understanding. Yet they're under great pressure legally, 'cause they need to be offering and doing more for these patients. Finally, you know, we've created significant infrastructure that will help, first of all, keeping people in treatment when they want to remain in treatment, whether that be transition of care, whether that be help with funding. Again, very, very important aspect. I'd just like to close out and say, I think, Matt, I believe we're moving to a Q&A. Okay. Thank you very much. Okay. Thanks to the team for that great overview on our number 1 priority, which is SUBLOCADE to greater than a billion and a half of revenue. I think it's a unique opportunity for Q&A on this matter. We've got the members of the team that are delivering against this strategic priority here. We're gonna try and limit this round of questions to about 15 minutes and solely on SUBLOCADE. We'll get the rest of the program, including the operating model and midterm guidance, we'll handle at the Q&A at the end of the session. If we could just go ahead, and as you ask your questions, please provide your name and your affiliation, and then I'll work with the team to have them help answer the questions. Can you give me your mic? It's Max Herrmann from Stifel. Just thanks very much. Got a few questions. Firstly, just in terms of the conversion and the market penetration that you're expecting for SUBLOCADE, I think you talked about getting to a sort of around 10% share of the market, what today's market is, but also you're actually referring to where you'll be. Mm-hmm. We don't know exactly when, but in the future, and obviously that's a growing market. Trying to really understand what type of penetration that really means, first question. Secondly, I know obviously BRIXADI has been launched throughout Europe. I believe in certain markets you've seen, I think, in Finland, about 50% conversion of the buprenorphine market to long-acting injectables. I wonder what, you know, what you get from that in terms of, you know, what sort of market penetration is possible and why that differs potentially in a market like Finland, Scandinavia, compared with the U.S. Just in terms of the criminal justice system, you know, how have the views changed there? Obviously, a few years ago, you were talking about the criminal justice system being absolutely against any type of opioid treatment. We're starting to see buprenorphine products being used. Just how the attitudes are changing, how widespread that is, and where do you think that will end up as well? Now- Kinda longer term. Thank you. Thank you, Max, for the questions. Maybe what I'll do is I'll handle the BRIXADI question. then I'll hand it off to Richard to talk about how we see the market and the factors that are impacting that moving forward. I'll hand to Vishal to talk through the criminal justice system and the mindset. He's out there on a day-to-day engaging with these systems. From a BRIXADI standpoint, the fact that there are some markets that have a deeper penetration, each market has a different treatment sort of paradigm. I think the U.S. has a very unique paradigm that we're looking at. historically, we've talked about there's market research that say patients or physicians could see up to 30% of their patients on long-actings. We've seen in schizophrenia, where about 20% of the market has transitioned over to long-actings. Where will the actual market get to as we continue to normalize this treatment towards long-actings? It's a tough one to call on exactly where it is, but every market's different. You know, you have Finland, which is over 50% on a very accelerated path. We'll continue to talk about the benefits of both long-actings as well as our unique product profile that we don't see getting matched by other long-actings in development, and do our best to bring it out to more and more patients, so they can enter recovery. With that, I'll hand over to Richard, you know, to handle the question with regards to the future. I think your question is to do with market share and the 10%. If we go back and remind ourselves of the numbers today, there's about 1.8 million people in treatment within 12 months. We see that moving to about 2.8 million by towards 2028, 2029. The 10% share is really based on the 270,000 patients we believe that we're getting into treatment based upon that, those two numbers. Vishal, could you address the criminal justice system and the mindset change that you're seeing? Thanks for the question, Max. Mindsets are shifting, as I referred to in my presentation, and also Dr. Santoro said, over the years, the mindsets are shifting. The tone has been set really at the top, where President's Unity Agenda really calls out addiction treatment right at the very heart of what we're trying to do. Whilst I wouldn't say that it's been a complete sea change. It's an evolution. We are starting to see major systems, major decision-makers, and also the mandates that are going in place to ensure Medicaid-assisted treatment becomes available in all forms of. That change has started and the evolution has started. I might, I might add to that a bit. You know, the other thing we're seeing is not just at a federal level, but at state levels. You've got states such as New York, which have mandated having treatment while you're actually behind the wall. That's really, for me, a gold standard, so that you can intervene at a moment where they've had a life-altering event, a moment where they're very receptive to treatment and trying to transform their life. We see New York as a bellwether, and we're keeping a close eye on it as we know a lot of other states are. Those are just a few indicia of how the mindsets are changing in an area where patients just weren't getting treatment historically. We're seeing this moving, this mindset. Next question, please. Hi. Thanks very much. It's James Vane-Tempest, Jefferies. A few questions for you. On SUBLOCADE, helpful information on volumes you've given. Just curious what you're thinking about pricing over the period and how would you think about makes. I'm just wondering whether criminal justice system may come at a discount. The second question is, the proportion of physicians you mentioned with waivers was, I think, 48.6%. You mentioned there were some reasons why they're not prescribing. Just wondering if you can go into some of the details why that is. Can you remind us as well any circumstances physicians may be able to see more than 30 patients, and how we should think about that as well? Third question is the 1.8 million-2.8 million patients. How much of that do you think will actually go to generics? When you think about expanding, you know, the overall market, how much of that would go to SUBLOCADE just given the pricing differential? Final question is on the criminal justice system. VIVITROL's obviously been quite successful there. I'm just sort of wondering whether you're expanding the overall market or you're taking share or a combination of the two. Thank you. Thanks, Jamie Swain. I think I'll deal with the volume question, volumes versus price. We'll ask Richard Simkin to handle the waivers and the instances of when it changes from being able to go to 30 patients to having to have a waiver, as well as the, you know, essential generics versus branded. And then I'll ask Vishal Kalia to handle the VIVITROL question. When it comes to pricing, you know, we've got unbelievably strong coverage, national coverage, over 88% of lives, you know, that are covering SUBLOCADE. This, for me, is a very strong result, and so access is not a barrier to treatment. In addition, you know, Vishal Kalia had talked about the co-pay program that we've put in place, that for commercial patients, it buys down their co-pay, you know, to potentially $0. So price isn't a barrier with regards to that. Now, as we look at the dynamic moving forward, obviously the government accounts have a mandated 23% discount that's there. And the majority of our patients, in excess of 50%, are in these government accounts. And as you mentioned, Jamie, in the criminal justice system, they get government pricing. So as we acquire patients in criminal justice, there could be a mix shift, but from a pricing standpoint, you know, we think we're in a relatively stable environment. Richard, would you like to talk about the waivers? Yeah, certainly. The waivers. Just to remind ourselves, there's about 120,000 healthcare professionals today able to prescribe, but within there are different levels. Some can prescribe up to 30 patients, up to 100 patients, or up to 275 patients, depending on their sort of like status within that waiver. That's one differentiator. I think the second question you asked was to do with why only 48,000 of the potential 120,000 are actually prescribing. That really goes back to the disease and the stigma and some of the challenges. Unfortunately, there's a lot of practices that don't want to treat these patients here. These are very difficult patients. They're not rewarding patients to some degree. They're relapsing. They're coming in. They're coming out. Sadly, it's a challenging disease space, and I think a lot of practices don't want to do that. I think the other area is that we saw people signing up for the waiver, so a nurse practitioner or a physician's assistant working with another healthcare professional, and then we see that they're not actually doing anything. They've moved jobs. They didn't want to do it. They were uncomfortable. Various reasons, really. I think the key point here is, you know, there's a great opportunity to close the treatment gap by accelerating those people that are able to prescribe and that are wanting to prescribe. Again, normalizing and destigmatizing is critical at the heart of really unlocking the potential. Thanks, Richard. Vishal, if you could cover criminal justice, I'll talk about in the future the impact of generics that. Thank you. was Jamie's last question. A couple of points of reflection on that. I think the first is, as I referred to earlier, we believe the market for treatment is very large and different, and also the mindsets are shifting with regards to more and more treatment being available across different systems. We believe, and it goes in line with our philosophy, ensuring various forms of MAT is available, and for providers like Dr. Santoro to then make the recommendations what's right for the patient. We believe very confident in our plan. We have the right orientation and the right ideas and implementation to ensure we can make access available. Thank you. Yeah. I think the key there is there's so few patients getting treated in the criminal justice system that a big percentage of this will just be new patients getting treated. To your last question, Max, with regards to as we move forward and the market expands, is there a price sensitivity with regards to the generics? I think I talked to that in my first answer with regards to the access of coverage. You know, the real low price point for patients, so there's not a barrier to entering. We don't see price as a major issue. If you look in schizophrenia, it's highly genericized. It's been growing, you know, over a period of time, and there just hasn't been a barrier, you know, to patients getting online in that market. Okay. Thanks, James. Any other questions? Oh, there's one. Hi, it's Christian Glennie with Stifel. I guess, just remind us in terms of the duration of treatment here, that you're seeing on Sublocade versus the film and whether that's continuing to expand or have we reached a certain level in terms of how long these people are on Sublocade. Follow-up to that, in terms of the reasons why they stop, you know, is there any evidence around, you know, they actually are moving on with their life, they've managed the condition or they just are going back on? Thanks, Christian. I'll handle the duration, and then I'll hand over to Richard to talk about why is it patients are stopping and their first question when they enter treatment. From a duration standpoint, we've seen an average duration has increased and ticked up just a bit since launch. You know, we were at about four and a half to five months duration at launch. We're kind of in the five and a half or so range now. In our billion and a half dollars, we've not factored in any increase in length of treatment. Christian will share with you a bit later when he goes through his real-world evidence and scientific sort of generation behind SUBLOCADE, his RECOVER study, which talks about the benefits of a longer duration in treatment. These are patients who on average, have abused for six years before they enter. Their brain and reward system has completely rewired, and they need to maintain, you know, that sense of stability for a period of time to get their psychosocial counseling and truly have a good chance in recovery. Richard, you wanna talk about the dynamic of patients coming out of that treatment? Yes. I think understanding a patient, typically the first question a patient will ask a physician is, "When can I stop taking the medication?" They still view it very much as an acute problem rather than a chronic condition. I think the first challenge is when can I stop taking, so you're dealing with that. A lot of times, they're also getting family pressure about coming off the drug as well. That's the backdrop to it. Mark spoke about it's actually quite a stable base that we see really. With regard to that, it comes back to again, destigmatizing, letting people know this is actually fine to be on. Again, like a chronic condition like diabetes, the first question you're asking is when not when can I stop. I think, you know, those are the areas that we're working on. When Christian really gives his speeches and you'll hear some of the work they're doing. He's doing some great work. They're trying to understand how well do they recover once they stop taking it, and are there any insights that we really get from there that will start to trickle down into the community. Yeah. Yeah. That's good. Listen, people think an opioid is an opioid is an opioid, and they don't realize the pharmacokinetics, the different profile that buprenorphine has that makes it a WHO essential medication for moderate to severe opioid use disorder. Christian will talk about those unique characteristics in his scientific section. I won't steal any of his thunder by going into that now. Harry Hares at Numis. Just to follow up on that. Sorry. Go ahead. We can hear you. What are the side effects that patients experience from SUBLOCADE? How does that affect the way that they continue their treatment? That's a great question, Harry Hares. I'd ask Richard. Why don't you go ahead and share the mic with Christian, you know, who understands completely kind of the adverse event profile. He has the call center that manages those as they come in. Christian, could you talk to those? Yeah. We currently have a really good safety profile. The only thing that you see at the beginning of treatment are some injection site reactions, which is completely normal for an injectable of that sort. These original side effects are actually resuming over time, significantly decreasing over time. There is certainly no drive there to stop treatment due to any side effects. We have a very, very safe profile. I think the other thing to remember, Harry, is these are not patients who are typically needle naive, right? Just based on the nature of the disease space in which they've been engaged. While there are some minor adverse events early on, they're not a barrier to treatment, typically. Any other questions before we take a 15-minute break? Oh, there we go. Jamie is back. Thanks so much. Two follow-ups, if I can. The more than GBP 1.5 billion, how much do you need to spend on further education, how material is that to you guys? My understanding is sometimes patients perhaps don't want to take SUBLOCADE because they're worried it's not gonna work. They're kind of used to having that kind of daily check-in, and if they don't, they're worried they might relapse, then they get a positive experience afterwards. My second question is, can you give us a feel into how much of that will be of the $1.5 billion versus rest of the world? Just given the fact that you talked about, I think 36 countries for SUBOXONE in 12 for SUBLOCADE, how material that could be as we look out over the horizon as well. Thank you. Thanks, Jamie Swain. I think the education is a key. I think it's built into the base assumptions that we'll talk in the operating model that Ryan Preblick will provide some more granularity. The really robust, unmatched scientific generation that Christian Heidbreder has, his team, both the R&D team, the medical team, take that to disease state conferences, really educate with regards to those, the papers that are put out. Of course, the medical science liaisons whose job it is in a very compliant fashion to engage on the new breakthrough science in the disease space. There is a big component of it because this science is transformational, but it's built into the base. I think your second question was with regards to the U.S. versus rest of world. Richard Simkin, you wanna talk through that? Yes, certainly. I think the numbers you saw there really were predominantly the U.S. I think the rest of world is a great opportunity, but as we highlighted earlier, U.S. really is where the majority of the opportunity sits. The $1.5 billion really is driven by the U.S. I think for us, it's the rest of world is just increased confidence on why we say it's greater than a billion and a half dollars. All right. With that, it's 10:11 A.M. Jason, how long would you like to break for? I just think easy everyone get back in at 10:30. Okay. To 10:30 A.M. then. Thank you, everyone. Good morning. My name is Glen Tyson, I'm the Senior Vice President of Sales and Marketing. I'm here today to talk about PERSERIS, I'm happy to do it. PERSERIS represents a meaningfully differentiated product in the category, we believe that it represents a meaningful diversification opportunity for the company. PERSERIS is targeted to achieve $200 million-$300 million of net revenue at peak. We believe in this potential. We're gonna talk today a little bit about why we're so confident in that. It comes in three areas that we're gonna talk about. One is that it's attractive, growing, dynamic market. Two is that we are gonna be leveraging a highly differentiated product profile that provides real benefits to patients and the clinicians that treat them. Lastly, we'll be diving into a little bit around the executional excellence, which really gives us the confidence of where we are today and why we believe that we'll be able to achieve the $200 million-$300 million net revenue. Sorry. First, let's talk about the market. For those of you that are aware, every market entrant that has come into the long-acting injectable market has helped to drive up the growth, the rate of growth within the market. You can see over the last 20 years or so, all of the products that have come into the long-acting injectables for the treatment of schizophrenia. Each one, as it's come in, has also contributed to the growth. You can see that when PERSERIS came in and the growth continues there, we believe that the growth will continue, and we'll talk about some of the reasons why in a few moments. The five-year CAGR is about 18%. Excuse me, 15%, and that's representative of partially due to volume and partially due to value. That being said, with the market growth and now approaching almost $5 billion, it is still a very low penetration rate. What we mean by that is the number of patients or the percentage of patients with schizophrenia that would be appropriate for a long-acting injectable and therefore suited that are on a long-acting injectable is only about 18%, and that's calculated based upon patient months in the units that we see in the market. There still is great room for penetration here and another reason to believe in the category. It is not a generic market at all at this point. All the products that are in the long-acting injectable space are branded. The market is divided largely into two molecules. I'll talk about the differences here in a second. First is the risperidone paliperidone side of the house. Why do we group those together? Well, that's because paliperidone is the active metabolite of risperidone. In the case of PERSERIS, which has risperidone as the active, after metabolism, it breaks down into paliperidone and risperidone. Paliperidone is the active metabolite of risperidone, and therefore we categorize the products that have that as the active in the same bucket. Risperidone, paliperidone, and the aripiprazole patient is also there. What's the difference between the two? Well, they're both effective medicines for the treatment of schizophrenia. There are different aspects of the medications that are attractive to the clinicians who are trying to treat, let's say, the positive symptoms of schizophrenia. What are the positive symptoms of schizophrenia? Those are the ones that you would most commonly associate with schizophrenia. That being hallucinations, delusions, paranoia. Those are the things, the positive symptoms of schizophrenia that are most well treated by risperidone. That's what's understood in the market, and you can see that in the way that it's utilized. That is why you see that the risperidone, paliperidone side of it is a larger share. Within that side, there are a fair amount of competitors. We are sixth to market. We are a challenger brand in this space, we're certainly not the market leader. We're a challenger brand. There are well-established products on this side. You can see them there, RISPERDAL CONSTA in the Invega family. On the aripiprazole side, there are two products there. It is ABILIFY MAINTENA and Aristada. PERSERIS is competing in the overall market, you can see here that it's advantageous that we're in the largest side of the market where we have clear differentiation between the products that exist, we'll get into that differentiation shortly. Another attractive part of our story here is really that in the one-month LAI category. You could ask, you know, what's happening with the various different durations of treatment for some of the other LAIs? The LAI portion of the market is the lion's share of it and growing. In 2015, once monthly long-acting injectables in schizophrenia accounted for 68% of the market, and today it's 84%. It's really important that we understand the patient. I think at Indivior that is really high on our radar is to deeply understand the patient insight, the patient journey when thinking about how we translate the needs and the challenges there to a pharmacokinetic solution in the form of our medicines. Which is exactly what we've done both in the case of SUBLOCADE and PERSERIS. The life of a patient with schizophrenia is tough. Starting at age between 18 and 23, when the initial diagnosis is made, it is characterized by periods of stability and instability that go on throughout their life. As they age and they get into later part of their life, some of these symptoms abate. During the majority of their life, they are faced with periods of stability and instability. Instability, you hear me refer to it as a psychotic episode or as a decompensation episode, so you'll hear those terms throughout the presentation. When they decompensate, and those are the red dots on the screen there. When they decompensate, what does that mean? Well, they usually end up in an emergency room, or they'll end up being picked up by the police. Someone who's ranting and raving down on the street corner, threatening people. That is when they're in a decompensated state, when they're actively psychotic. At that moment in time, when they're actively psychotic, the needs of that patient are to achieve stability quickly. Achieve stability quickly. Get them stabilized, usually in a hospital stay of 5 days to 7 days. Get them stabilized and then send them back out the door into their living arrangements, which many times are a residential situation that's supervised, or they may be the adult child who's disabled living with their parents. That gaining stability quickly is super important. One of the characteristics of this disease that really mitigates against their stability is actually a part of the disease which about 80% of patients with schizophrenia have, and that's what's known as anosognosia. Anosognosia simply means a lack of insight. As an example, for those of you in the audience who have... You have a medication that you're on, maybe you're on Lipitor, maybe you take something for blood pressure. We have garden variety non-adherence, right? You forget to take it. You've gone on vacation, forgot them sitting on your shelf. That's garden variety non-adherence. We all suffer from that. Patients with schizophrenia, because of this lack of insight, they'll believe that they're cured when they're on their medication, so they stop taking it. They'll believe they're being poisoned, perhaps by their clinician, so they'll stop taking it. They'll not show up for appointments. That characteristic of disease makes non-adherence in this category for these patients far worse of an issue than it is for many other categories. When they don't take their medicine, they end up where one of those red dots are. They decompensate at some point they're back, usually hospitalized or in some type of a highly supervised setting. The objective for treatment in this category is to maintain stability. Achieve it quickly, maintain stability. PERSERIS, as you'll learn, is really well suited for this opportunity because of the nature of its pharmacokinetic profile, which we'll get into in a moment. It's really well suited for the opportunity. It's important to keep in mind the objectives of treatment here, which are, number one, gain stability quickly and then maintain it over the longest period of time possible for these patients. The antipsychotic market is highly dynamic. It's highly dynamic because these patients have real challenges with adherence. When the patient re-presents to a clinician, they're in need of treatment change, right? They've gone off their medication or the medication potentially wasn't working for them. In either case, they're in need of a treatment change. This is from some market research that we conducted. You can see that when clinicians are surveyed, they say that within the next six months, the vast majority of their patients are likely to need a treatment change. The slightly likely is 24%, somewhat likely 21, and very likely 17. There's a high level of understanding within the clinicians that treat in this space that patients are going to have challenges and they're going to need to consider a treatment change, whether that means they've gone off their meds or the medication they have is not sufficiently working to manage the symptoms. Keeping on the theme of the dynamism in this market, let's just take a look at what that means in terms of how it translates to prescriptions. The new prescription portion of the overall market represents almost 1 million patients a year. 1 million patients a year. It's 42% of the total market. 1 million prescriptions a year, rather. That means that every single one of those times that that patient, that a new prescription is written is an opportunity for a treatment change. The clinicians are considering those treatment changes based upon the attributes of the products that they see, matching it up to the concerns that they have with their patients and keeping in mind here that many of these patients have been decompensated because of the lack of insight and the fact is what's presenting then are the positive symptoms of schizophrenia, the hallucinations, the delusions, and the paranoia. In fact, if you talk to a parent of an adult child who lives with them, they'll tell them they know when their son is decompensating because they disappear. They stop bathing, they stop having any kind of contact because they're super paranoid, and they'll be in a closet in their room or they'll disappear out the door and be living under a bridge. That's what happens with these patients. Therefore, they really have to be sensitive. Clinicians are sensitive to seeing the signs of when a patient is in need of treatment change. The new prescription part of the market is large. We also know that when it comes to PERSERIS, where we're sourcing our patients from, and just we're sourcing patients 65% from orals. That's no surprise, right? 65% from orals because the oral patients that are on just oral medications are many times not adherent. Many of the patients that are coming to PERSERIS are coming from orals, and that's characteristic in the market as well. There's also a fair amount that are coming from other long-acting injectables. And for, again, various reasons. All products in this category work, right? I think at the end of the day, we're not casting aspersions on the competition. What we're saying is that there's limitations to some of these other products. When the patient comes in and they're in need of treatment change because they're getting breakthrough symptoms, or they've decompensated, it is time to do that. That's when it's time to consider PERSERIS. It's in that moment that our sales team is out there trying to talk to doctors to help them understand the unique product attributes of PERSERIS that really can help in that specific instance. Lastly, on this slide, what we're starting to see is what you would hope to see, is that clinicians that have experience with PERSERIS use it more, right? They're starting to see a significant share increase for the clinicians that use PERSERIS. What you look at the 3 bars over here, I know it's kind of small type and probably even hard to read, but the left-hand bar, the 1%, that's our new prescription share, NRX share. The 2.5% is the NBRx share, the new to brand share. The 6.3% is the market share, the new RX market share within the clinicians that have used PERSERIS. You're starting to see more of a pickup in the clinicians that have used it because they're gaining experience. Our challenge then becomes, how do we gain more clinicians to trial it? We'll talk a little bit about where we are exactly with that in a moment. Once we do get in front of a clinician, it's all about the differentiated product profile. Why would they care, right? They have five other products, six other products out there. Why do they care about Prosaris? That's what our story is, and that's what really gives us confidence 'cause what we know about the product profile and how it really can meet the needs of the patients in this category. It's a compelling value proposition, and it really aligns well with the challenges that we've talked about so far in this presentation. We believe that when there's no time to waste, it's time for Prosaris. That is kind of our core selling message, if you will. It's really about that in that moment when that patient is decompensated and you need a treatment change, you should choose Prosaris. Our clinical trial design, our phase three trials, was designed just like that. We had clinic patients who were recently decompensated, and then they were put on PERSERIS in the beginning of the trial. We have a strong claim as to why our PERSERIS is effective there. It's effective there because it's got the molecule of choice for treating these symptoms and because we know that there's a number of product attributes that really make it attractive for the clinicians to use there. Number one is it's subcutaneous. It's the only subcutaneous long-acting injectable in this space. What does that mean? That means that it can be potentially less painful 'cause you're not sticking a long needle into the muscle. All of the other products in the category are intramuscular injections. It's got an innovative delivery system where it delivers an initial peak plasma concentration in 4hours - 6 hours. You're getting clinically relevant levels on day one. It's designed to reach and maintain target D2 receptor occupancy, dopamine receptor occupancy levels, you know, once it achieves the plasma concentrations. What's important about that? Well, the most important thing here is not the dose that you select. It's the choice of your medicine that achieves the target plasma concentrations of dopamine D2 receptor plasma concentration. In this case, in the case of SUBLOCADE, the objective there is to achieve greater than 2 nanograms per mil with a 70%-90% mu-opioid receptor occupancy. In the case of PERSERIS, the objective is to achieve a 60%-80% D2 receptor occupancy. See, because in the disease of schizophrenia, it's not about agonizing, it's not about creating more dopamine, it's about antagonizing the receptor and creating less 'cause there's too much circulating dopamine. That's the theory. That's the objective here, is to achieve that target plasma concentration of 60%-80% D2 receptor occupancy. We don't talk a lot about the dose so much as we talk about the target plasma concentration you're trying to achieve to achieve that result. Our clinical trials bore that out. In our clinical trials, we treated a markedly severe patient population who were exacerbated, then we gave them PERSERIS, and we have substantial efficacy results to show for it. Once it's reached and maintained those target dopamine, that's what you wanna do, is make sure that it maintains it for the entire month. Again, that's what PERSERIS does. A unique attribute of PERSERIS is that there's no loading dose or supplemental oral, no oral supplementation required. What does that mean? All of the products in the category require oral supplementation or some sort of loading dose, which you'll see in a moment. Then it's really important that it's a safe product, right? With the balance of safety and efficacy, this is a known molecule. This is a known molecule. It and this is great to know that just like with SUBLOCADE, the systemic safety profile is consistent with the known safety profile of oral buprenorphine. In this case, systemic safety profile is consistent with the known safety profile of oral risperidone. The only other safety issues that you or the side effects you may have is, as was already alluded to, maybe some injection site reaction, but you would get that with any long-acting injectable. Just to summarize. It achieves and maintains therapeutic plasma concentrations for the entire month. D-two plasma concentration of 60%-80%. Product profile that it delivers rapid and sustained target concentrations. Significant efficacy against therapeutic targets of interest. What does that mean? Well, we're trying to affect a positive effect on these symptoms of the positive symptoms we've discussed and this favorable risk-benefit profile. Let's talk a little bit about that differentiation. As I mentioned. The PK profile offers unique benefits. What you see here on the first line at the top there is PERSERIS on a weekly basis, what's required in terms of initiation with the product. The answer to that is nothing is required. You get the initiation of the product without oral supplementation or loading doses are recommended. Whereas every other product in the category requires some form of oral supplementation or a loading dose. Again, it's not to say those products don't work, right? We're not saying that here. We are saying that this may present a unique advantage when it comes to choosing PERSERIS, because you do not have the burden of having to have the patient who already is non-adherent taking oral supplementation while they're trying to get to the appropriate plasma concentrations with the long-acting injectable that you just gave. We see this as a distinct advantage of Proseras. It's the only product in the category that can make this claim. Sorry, these buttons are hard to see on this. It meets key LAI initiation needs. I think that's what we've already discussed. When we surveyed HCPs about the unique LAI challenges they have, that it's critical to achieve plasma concentrations early. Simplifying the LAI initiation regimen could lead to better outcomes for their patients. The need for oral supplementation for LAIs is a significant burden. There's wide agreement when we survey our target clinicians about this. These are areas where Proseras really has a distinct advantage. These differentiated messages we've put into our materials, and these are the ones that are seen as most motivating. When we tested these materials, with clinicians, we could see that this drove a high likelihood to prescribe. A high likelihood to prescribe. You can 76% likely to prescribe, and you can see the data represented there on the right-hand side. Just to summarize here, we have a differentiated product profile. Again, we're a challenger brand, right? We're not the first to market, we're the 6th. We're a challenger brand in this space, the way you need to cut through is to deliver a differentiated message, and that's what we believe we have here. It's not just because we've made up some marketing messages that sound nice because they are absolutely linked to the pharmacokinetic profile and the scientific underpinning of the rationale for the disease. To treat the disease with an LAI. It's just down to execution, right? It's just down to execution. You say, "Glen, if this is true and you have such a great product, then why aren't you already at 20 share?" We'll talk a little bit about that here, right? We're making some great progress, and we can see the fruits of our labor coming out in the way that this is translating into our, the results we are seeing. We'll talk about that now. For those of you that are aware, we did have a targeted launch, a regional launch, in the beginning of 2019. February or March 2019, with a small sales force. We launched that, and we could see that we were already starting to get some good uptake, and then COVID hit. COVID hit disproportionately, that disproportionately affected this disease space. If you just think about the offices that these patients are being treated in. Just envision this. Let's say all of you are in the waiting room of the office, and the office is 1/3 of the size of this room. That's what an office looks like, a very busy office with treating seriously and persistently mentally ill patients. They had to slow the flow of patients coming through that office and move to much more of a telemedicine model. Patient volumes then were managed that way. Imagine then you're trying to launch a new product and get face time with the clinician who now is in telemedicine or doesn't have time for you because their schedule is so replete with all the patients they have to see in this really considered manner, and COVID restrictions are in place. You're trying to launch a product in that environment, it can be challenging. We see that reflected in the results that happened during the COVID period. As we started to come out of the COVID period, we made the decision to expand the team, and that's what we did. More than double the size of the commercial presence to a national footprint with the objective meaning to cover more of the market. You can see that there, and cover more of the volume. As a result, we're starting to see the uptick. We still have some COVID restrictions in place that at the beginning of this year. We believe now we're starting to gain the traction that we hope we're getting, but we believe we're getting that back on track to what we expected it to be. That's why we are confident in achieving the $200 million-$300 million peak net revenue. Understanding that we, you know, it's one thing to know who the physicians are, who we need to go to. It's another thing to understand and kinda disaggregate the treatment model. Understanding exactly where the ecosystem, what it looks like, and where to weigh in. Just, again, giving us confidence here in achieving our expectations is really around understanding this marketplace. It's a different ecosystem slightly than what you heard about earlier with SUBLOCADE. It's a different ecosystem. Here, you have a lot more inpatient hospitalization versus, say, residential treatment centers because these patients, as already described, once they decompensate, that's where they end up. They come in the hospital, they may go to a crisis stabilization unit, which is a lower level of care, but patients can still be admitted there directly. They go back to their group home setting. They may be getting outpatient services from a different provider, or they're going to an assertive community treatment program. ACT programs are federally funded programs designed to help patients with serious and persistent mental illness. Many of these patients end up flowing through these types of facilities. Understanding this and then putting the right commercial model in place to address it is what we've done. We have some of our of the team that's in place are institutional specialists designed to go to those non-retail, the hospital and crisis stabilization units. We have the clinical specialists that are calling on the clinicians in all of these locations as well. That's the commercial model that we have in place and that we've deployed with the expansion at the beginning of this year. We have the understanding of the market. We have an understanding of our profile. We put those materials into a compelling story. Is our team actually delivering it? Well, I'm happy to say that when we use IQVIA BrandImpact to help us understand exactly what's being said within offices. This is third-party market research that's conducted on a monthly basis. What we can see is that on average minutes per detail, percentage of calls with compelling close and commitment to action, primary message differentiation, and primary message is relevant to the patients that I treat on all of those vectors. Our team is leading the market according to this market research. Very positive result for us, giving us, again, faith and confidence in all the hard work that we put into preparing the team, understanding the market, understanding the needs of the patient, and that we would then deploy that in a way that would be effective. As we've already discussed, this market is large and dynamic in terms of the prescriptions that are generated. This just gives you a sense of the patient population. Now, this is not a growing market in the sense that, you know, we're gonna see rapid increases in the number of patients with schizophrenia, because over time it's always about 1% of the market. As population grows, so too will the patients with schizophrenia. It's about 2.8 million patients with schizophrenia in the United States. There's about 60%-80% patients in treatment as reflected here and the number of patients that are on LAIs. But again, it's about market penetration, and I think that there's a huge opportunity that continues to be here as we move forward. We're confident in delivering the $200 million-$300 million peak net revenue for the reasons as discussed. We're understanding the top five drivers of prescribing. We're delivering a compelling message that has differentiated product attributes that are seen as valuable to the clinicians as well as patients. Once they understand them and hear them with the right level of frequency, so it's getting to those customers as we're doing, and we're seeing more and more of that now. One of the things I'd like to say is that our retention of HCPs once they've written is also very high. Not only once we get to them that they start to prescribe it, then we're retaining clinicians month-over-month, which I think is really important. What are the building blocks that get us there? We've talked about our confidence and why we think we can get there with the product profile and the attractiveness within this growing market. The building blocks that we're sharing with you today are four areas that we're looking at. The number of HCPs writing. This is where we are today, and this was what we believe is required, will be required at peak. The number RX per HCP. It's 15 today and 36 at peak. The TRX market share. Right now we're at that 1% we talked about, and we need about 7.5% at current market growth rates to achieve our... the midpoint, by the way, of our $200 million-$300 million target. The annual number of patients growing from the 5,400 that we have today to 40,000 at peak. In summary, PERSERIS represents an attractive long-term growth opportunity, both in terms of being differentiated in the market and providing us with a diversification opportunity within the U.S. It's growing branded market with 15% CAGR year-over-year, or in the last five years, and it's a branded market. As I said, there are no generics in there as of yet. The PERSERIS is significant differentiation that is meaningful to our customers and to patients in meeting the real needs of the patients in their understanding of their patient journey. We're delivering with commercial excellence as outlined by some of the market research that we shared with you today. We're mapping to the existing dynamics of the market, and we put a commercial model together to address them. The path to achieving sales, this objective is clear. The expanded team is now in place and settled in this year, we believe that as we move forward into next year, we'll only continue to have the type of success we've just started to see as we've gotten through this year. With that, I'll thank you very much for your time and turn it over to Christian. Good morning. My name is Christian Heidbreder. I'm the Chief Scientific Officer at Indivior. The objective of my presentation today is fivefold. First, I would like to introduce you to our R&D organization as well as the Medical Affairs and Safety organization, our philosophy and vision, strategic focus, and the current pipeline. Second, I will take you through some of our key projects to actually create and disseminate new evidence in support of SUBLOCADE as a treatment of choice for opioid use disorder. Third, I will remind you of the scientific foundations of PERSERIS. Fourth, I will review our current pipeline, starting with the AEF0117 in partnership with Aelis Farma for the treatment of cannabis use disorder. INDV-2000, which is aiming at becoming the first non-opioid medication for the treatment of opioid use disorder in a partnership with C4X Discovery. INDV-1000 in partnership with Addex Therapeutics for the treatment of alcohol use disorder. Last, I will share with you how we are currently identifying key receptor systems and potential drug targets in large-scale neural networks to prepare the medications of tomorrow and further grow our pipeline. Let me start with the first part, an introduction to Indivior R&D and Medical Affairs and Safety. As you can see, we currently have 108 employees in the research and development organization split into four main functions: chemistry, manufacturing and controls, global medicines development, including all non-clinical and clinical aspects of drug development, global project and portfolio management, and the last but not least, global regulatory affairs. We also do have 79 employees in the medical affairs and safety organization, split into three main functions. The global medical safety function, as well as medical affairs in the United States, and medical affairs in most of the world, including Canada, Europe and Australasia. We do have hubs in Richmond, Virginia, Fort Collins, Colorado, as well as Hull and Slough in the United Kingdom. We do have long-standing innovation leadership in addiction medicine from the very early discovery and synthesis of buprenorphine at the Reckitt & Colman labs in Kingston upon Hull. Leading, at the end of the day, to several medications for opioid use disorder. You can see here SUBUTEX and SUBOXONE tablets, SUBOXONE film, and more recently, SUBLOCADE. We also have a strong support and experience in label updates and extension, geographical expansion in most of the world, pipeline growth in addiction medicine. I will dedicate a section of this presentation to our current pipeline. Life cycle management studies, long-term collaboration studies, externally sponsored studies, real world evidence workstreams, and of course, quite a lot of peer-reviewed publications and presentation at international conferences. Our philosophy is very much aligned with all the materials that you have already seen today presented by Mark Crossley, Richard Simkin, Vishal Kalia, and Glen Gormley. Also with this very interesting publication that was released in 2019, entitled Medications for Opioid Use Disorder Save Lives. I would like to summarize here six important points from that publication. First, FDA-approved medications for the treatment of opioid use disorder are effective and actually save lives. Withholding or failing to have available all FDA-approved medications for opioid use disorder in any care or justice setting is denying appropriate medical treatment. A lack of availability of behavioral interventions is absolutely no justification to withhold these medications. Long-term retention on medications translates into improved health outcomes. Most people who could benefit from these medications unfortunately do not receive it, and access is inequitable, as you have seen from Richard's and Vishal's presentation earlier today. Last, confronting the major barriers to use these medications is absolutely essential to addressing the opioid crisis. I think that these are very, very important messages that are really at the core of who we are as an organization. Therefore, our vision as an R&D organization is really threefold. First, transform world-class science into life-changing medications for the treatment of substance use disorders and associated comorbidities. Second, innovate evidence generation based on insight, connections, and analytics, not only to better understand our approved medications, but also to inform the discovery and development of the medications of tomorrow. Last but not least, accelerate access to treatments by articulating not only the clinical value of our medications, but very importantly, their economic value. This is the realm of health economics and outcomes research, and I will show you a few examples of those later in the presentation. Our strategic focus is very clear, as you may have heard earlier today. We mainly focus on opioid use disorder, cannabis use disorder, and alcohol use disorder, mainly driven by the gravity of the epidemiology. Of course, we always keep an eye on other opportunities, including psychostimulants. I would say, especially these days, when some authors have referred to as the new twin epidemic, that is the co-use of opioids with stimulants such as cocaine and methamphetamine. We continue to look for additional opportunities in this space as well. This is our current pipeline. You can see in dark blue the currently marketed medications. I will spend a little bit more time in the next section to elaborate on all the life cycle management studies that we are currently performing. In light blue, you can see the three projects that we currently have in the pipeline. Again, one for cannabis use disorder, one for opioid use disorder, and the last one for alcohol use disorder. Let me move now to the second section, more dedicated to Sublocade. Before I talk about Sublocade, let me remind you of a few pharmacology basics to really understand why buprenorphine is so unique. Actually, if you compare buprenorphine with a broad range of opioid-based compounds, you can see that buprenorphine is very unique for two main reasons. First, it has a very high affinity at the mu-opioid receptor. Second, it has a very slow dissociation at that same mu-opioid receptor, and that's a very unique combination. Why is that important? Because it means that once proper concentrations of buprenorphine are on board, there is very little opportunity for illicit opioids to actually sit on that receptor. This is why buprenorphine, at the end of the day, has been very effective in quickly stabilizing patients but also managing withdrawal symptoms, craving, and very importantly, helping to prevent relapse or reinstatement of opioid-seeking and -taking behaviors. The scientific foundations of SUBLOCADE are really based on this critical relationship between plasma concentrations of buprenorphine and the mu-opioid receptor occupancy in the brain. Let me take a couple of minutes now to take you through why that relationship is so important. If there are no buprenorphine on board or very low plasma concentrations of buprenorphine on board, you are really in that situation. That is, very few brain mu-opioid receptors are occupied, which means that more mu-opioid receptors are actually available for illicit opioids. This is what you can see on that image there, the colors that you can see, the red, the green, the yellow, these are all receptors, mu-opioid receptors, that are currently available. That is not a good situation. Patients are at risk under that situation. If you now increase plasma concentrations of buprenorphine, and we determine that there is a minimal threshold of two nanogram per ml, that translates into a minimum threshold of 70% mu-opioid receptor occupancy in the brain. Now you can see a very different picture. What does that mean? It means that very few mu-opioid receptors are actually available for illicit opioids. SUBLOCADE is delivering these important plasma concentrations of buprenorphine consistently over the one-month duration treatment. Remember these pictures. At risk, no buprenorphine or very low buprenorphine on board. SUBLOCADE delivering the most appropriate levels of buprenorphine at a minimal threshold of 2 nanogram per ml and minimum 70% mu-opioid receptor occupancy in the brain. That is good, we had to demonstrate that actually this fairly unique pharmacokinetics profile translates into clinical efficacy, safety, and we went beyond by looking at patient experience, what we call patient-centered outcomes. Here are just a few examples of peer-reviewed publications. You can see on the left-hand side there, we demonstrated that actually SUBLOCADE can block not only the subjective effects, that is the drug-liking effects of illicit opioids, but also the objective effects, that is the actual self-administration of these products. We demonstrated clinical efficacy and safety after 6 months, 12 months, and 18 months of exposure to SUBLOCADE. Finally, we went beyond the traditional clinical endpoints that are required for regulatory approval, and we started to focus on patient-centered outcomes. Why is that important? Because recovery is not only about abstinence from opioids, it's significantly more complex than that. We started looking at the impact of SUBLOCADE on physical health, mental health, employment, the way patients reengage in their community. All those are critical factors to recover your life. This is what we have done in a series of studies, and there are just a few examples here. Last but not least, we were the first to initiate a study that we call the RECOVER study. In the RECOVER study, we were really wondering what is actually happening to patients when they stop treatment with SUBLOCADE, and we followed them over extensive periods of time. What we clearly demonstrated there is that the longer the treatment, the better, the higher the probability of recovery from this chronic disease. I will show you now a few examples of these studies we performed. We are in fact now moving to, I would say, a next wave of studies that are really now looking at the impact of SUBLOCADE on a broad range of treatment settings, but also, for example, adherence and long-term recovery, patients at very high risk of opioid overdose, non-fatal overdose. We don't speak enough about non-fatal overdose and the potential dramatic consequences of these non-fatal overdoses. I will show you a couple of examples of the potential impact of SUBLOCADE in the criminal justice system and the Veterans Health Administration. At the end of the day, what we have done here is a fairly multidimensional strategy, whereby we are working together on further label updates, long-term collaborations, externally sponsored studies, real world evidence work streams, life cycle management studies, and of course, we are publishing all that knowledge. I'm not afraid to say that we are currently building probably one of the largest evidence-based understanding of medications for opioid use disorder. Last but not least, you have seen with Dr. Horton earlier today, with Dr. Santoro, we are really focusing on patients' insights and advocacy to really further increase our understanding of the disease space and the available medications. Let me start with a couple of examples on adherence and long-term recovery. This is actually here on the left-hand side, what we call the RECOVER-Long Term study. Believe it or not, we are now at four years after a treatment with SUBLOCADE. We basically followed a cohort of subjects who actually participated in the original phase III trial. It has been on average now 4.2 years after they received their last SUBLOCADE treatment. What can we see? Well, I think that the most important message here is that you still see high level of abstinence from opioids, 74% in the past seven days, 60% in the past 30 days. That is quite remarkable if you think about it. There are two other things that we discovered, trying to understand actually what is the algorithm of treatment success. Well, there is very low odds of opioid misuse that is associated with improved quality of life, and treatment effectiveness. That is exactly what SUBLOCADE is doing. It is improving the life, the health-related quality of life, and that is measured by improved treatment effectiveness. It makes a lot of sense. However, we also determine that unfortunately, you have higher odds of opioid misuse if you suffer from depression, psychological distress, opioid craving and withdrawal, and opioid use disorder symptoms according to this DSM-V. Of course, that is unfortunate for all those patients who do not have access to treatment. Second example is coming from Australia. This is what we call the COLAB study. It's a real-world evidence study where we looked at patients who were actually treated with SUBLOCADE for 12 months. The main message here is that time retained in SUBLOCADE treatment was associated with, number 1, high retention rate. You can see 86% after six months, 75% after a year, improved quality of life and employment, and decreased odds, not only of opioids, but a broad range of other illicit substance uses. This is a very important study that we launched a few years ago, aiming at really understanding the pharmacodynamic interaction of buprenorphine with fentanyl in opioid-tolerant subjects. Why is that important? You have seen the epidemiology earlier today from both Mark and Richard. This is becoming now one of the main drivers of opioid overdoses in this country. What we did is to run these lab experiments in opioid-tolerant subjects to really understand the relationship between plasma concentrations of buprenorphine, the probability of apnea, that is cessation of breathing, potentially leading to death. That's unfortunately the drama with the opioid overdose. All that in relationship with increasing levels of exposure to fentanyl. Now, I do have a laser point that unfortunately is not working on this screen, so I will leave the microphone for two seconds just to show you the exposure to fentanyl. This is the exposure to fentanyl from very low levels to very high levels. What do you see on this graph? Well, you can see that unfortunately, when there is no buprenorphine on board or very low concentrations of buprenorphine on board, but for whatever reason you have been exposed to high levels of fentanyl, you have an 85% probability of apnea. This is absolutely dreadful, and this is what is driving right now the opioid overdose crisis. There is some good news, however. If you increase plasma concentrations of buprenorphine, especially to levels similar to those that are currently delivered by SUBLOCADE, and again, look at the threshold of 2 nanogram per ml and above, you can see that your probability of apnea decreases to 12% with 2 nanogram per ml, 5% with 5 nanogram per ml. By the way, 5 nanogram per ml is happening when SUBLOCADE is at steady state. 85% down to 5%. This is why we believe that SUBLOCADE is a treatment of choice for opioid use disorder, among other features. This is another example of what we are currently doing together with Dr. Kenneth Lee in Canada, looking this time at non-fatal opioid overdoses. In that study, we basically looked at three different medications for opioid use disorder. You can see Sublocade, there on the left-hand side, the BuXR, buprenorphine naloxone sublingual product, and then methadone. We looked at the incidence of non-fatal overdoses. I think that the graph speaks on its own. We saw very, very few non-fatal overdose events with Sublocade compared with sublingual buprenorphine and methadone. This was a retrospective study. We are now validating this very encouraging data with a prospective study that is actually currently ongoing. We talked a lot about the criminal justice system, so let me share with you a few examples of publications. This one has been driven by Dr. Josh Lee. It was published in JAMA Network's Open earlier this year, really looking at the impact of Sublocade versus sublingual buprenorphine naloxone in 52 incarcerated subjects. There are a few key messages there talking about the importance of transition of care and how we can actually facilitate that transition of care. You could see that 69% of subjects who were actually treated with SUBLOCADE had an opportunity to stay in a buprenorphine community treatment after they were released, you know, from the criminal justice system, versus only 35% of those who were treated with sublingual buprenorphine. You could also see that SUBLOCADE led to significantly better outcomes in terms of negative urine drug screen, and then significantly less reincarceration compared with sublingual buprenorphine and naloxone. Some very, very encouraging data. Dr. Josh Lee, actually, as we speak, is now working on a significantly bigger study to further refine and validate these results. This is another very interesting publication, more qualitative in nature, but they were aiming at interviewing subjects in the criminal justice system during the COVID-19 pandemic. Here are a few key messages that they wanted to share in that publication, that SUBLOCADE treatment clearly impacted interactions with peers and the criminal justice staff as well as their quality of life during and after incarceration. The treatment effectively eliminated social pressures to actually divert daily medications in the criminal justice system. It also mitigated quite a lot of COVID-19 potential exposures by eliminating daily contacts with the criminal justice system staff. It decreased the need to commute to either an inpatient clinic or to pharmacies. Some very, very encouraging results here. The last couple of examples I took here relates to the Veterans Health Administration. A very important publication here by Dr. Cotton earlier this year, really looking at 26 very clinically complex patients in the Veterans Health Administration system. You can see here a few key data. First, the retention was really high for that patient population. 81% actually received more than six injections of SUBLOCADE. Maintenance was very high as well. 77% were actually maintained on the highest dose of SUBLOCADE of 300 milligram. Then you can see the impact of a treatment on a series of parameters, such as a significant decrease in emergency department visits, hospitalizations, days of hospitalization, of course, use of non-prescription opioids and a decrease in homelessness. You can also see that the mortality rate was unfortunately quite high, as we typically see in that complex patient population. There were six patients, please know that five patients out of the six patients were not related to substance use disorder at all. All of those were also disengaged from treatment. The last one I wanted to present to you is actually not a publication of a study, but rather the publication of a protocol for a new study that is currently ongoing. This is a pretty big study, as you can see, 52-week, 20 sites. It is really going to be dedicated at comparing SUBLOCADE to sublingual buprenorphine and naloxone in a population of veterans. The primary endpoints will be retention in the medication as well as opiate abstinence. The beauty of the study is that it will go far beyond. There will be a constellation of secondary endpoints. As you can see here, the study will look at other illicit substance uses, psychiatric symptoms, medical outcomes, including prevalence rates of HIV, Hep B and Hep C, as well as social outcomes, housing instability, criminal justice involvement, and then, of course, healthcare resource utilization and the cost effectiveness of these two medications. Let me now move to the third section of the presentation and talk a little bit about PERSERIS. This section for me will be very brief because Glen has done an outstanding job of presenting to you all the background. Just reminding you of a few very basics on the scientific foundation of PERSERIS. As Glenn mentioned, the product or the formulation was really designed to deliver a very stable and appropriate concentrations of risperidone immediately after the first injection. You can see that quite clearly here, very stable level of risperidone, again, from the very first injection. As Glenn mentioned as well, the plasma concentrations of risperidone were also engineered to be within that famous 60%-80% dopamine D2 receptor occupancy in the brain. Why is that important? Because again, after several decades of research, we know that if you do not reach 60% of dopamine D2 receptor occupancy in the brain, you lack clinical efficacy. Unfortunately, if you go beyond 80%, you start running into side effects and typically what we call the extrapyramidal syndrome or pseudo-parkinsonism that you absolutely want to avoid. The key was to engineer the product to deliver these very stable plasma concentrations of risperidone within that bandwidth, 60% dopamine -80% dopamine D2 receptor occupancy in the brain. We also showed that unique pharmacokinetic profile led to clinical efficacy and safety. As Glen mentioned, the original phase three trial was in patients with acute exacerbation of their schizophrenic symptoms, and this is why the study actually lasted only four weeks, and this is what you can see there at the beginning of the graph. We demonstrated that after 1 year you stabilize these patients, and these are basically the flat lines that you see there on the right-hand side. This is exactly what you want to see to stabilize your patients over extensive periods of time. The fourth section now will be dedicated to the future and what we currently have in our pipeline, I will start with AEF0117 for cannabis use disorder, partnership with Aelis Farma. Before I talk about this molecule, let me give you a little bit of background. The latest data from the World Health Organization clearly state that we are now dealing with 209 million people worldwide using cannabis. That number of past year cannabis users has increased by approximately 23% over the past decade. If you look at the situation in the U.S., we are now talking about almost 50 million past year users of cannabis among people aged 12 or older. Unfortunately, we now have a pool of 14.2 million people actually diagnosed with a cannabis use disorder according to DSM-V. I would say that there are really four challenges in that disease area. Who says challenges also says opportunities. I will try to demonstrate what needs to be done next. First it is normalization of use. The latest data now clearly indicate that 37 states here in the United States, plus the District of Columbia, legalized cannabis for either medical use or recreational use. We also see, unfortunately, a new generation of products, very high potency, cannabinoid products. Actually, the potency of THC in cannabis, was about 4%-6% 20 years ago. On average now, we are talking about 17%-20%. The drama is also now access to synthetic cannabinoids. Those products may have a potency of up to 70%. That's a huge and radical change in the cannabis landscape. Second is presentation and diagnosis of the disease. There is still a lack of education and understanding of the symptoms that may actually lead to a cannabis use disorder. The third is the treatment and the management of the disease. Let's be clear, there are no therapeutic options right now for patients suffering from cannabis use disorder. There is no therapeutic option for acute withdrawal, there is no therapeutic option for acute cannabinoid overdose. There is a massive gap in the treatment landscape. Last, the maintenance and the follow-up of these patients, especially those who are not only suffering from cannabis use disorder, but from comorbid substance use disorder and psychiatric illnesses. There is absolutely no follow-up at all for those who are in that situation. I would say that the storm right now has four main components that may lead to cannabis use disorder. First, the increasing prevalence of use. Second, the increasing intensity of use in terms of both frequency and quantities. Third, the increasing THC content of cannabis products. Last, but certainly not least, the age of cannabis use initiation. A fairly scary situation. What are we going to do about this? This is when we met some scientists from Aelis Farma in Bordeaux, in France, under the leadership of Dr. Pierre Piazza. We got really excited about this new mechanism of action. I will try to explain this to you in relatively simple terms. Actually, what Dr. Piazza and his team discovered is that stimulation of the cannabinoid one receptor by THC actually increases brain pregnenolone. What is happening to brain pregnenolone when it is released? Well, the second big discovery that they made is that pregnenolone will actually bind onto that allosteric modulator site on the cannabinoid one receptor. That's a completely new discovery that nobody, you know, even thought about in the past. What is happening when pregnenolone actually sits nicely on that little allosteric site on the CB1 receptor? Well, it is going to block very specifically what we call the downstream pathways that are responsible for the intoxicating effects of cannabis, but not other downstream pathways. That's very important compared to what we call cannabinoid one receptor antagonist, that basically sit on top of the CB1 receptor. By doing so, they block everything. They block the pathway I was just referring to, but other downstream pathways. Unfortunately, by blocking these other downstream pathways, you start seeing a lot of side effects. This is really what we wanted to avoid. Now you may tell me, "Well, that's very simple. If it's just pregnenolone released, why don't you just inject pregnenolone? That should do the trick." You are right theoretically, but things are always more complicated than you think. Here we are again in that situation. Pregnenolone is not a druggable compound. What does that mean? There are three main reasons why you cannot do that. Number one, it has a very short half-life. Number two, it is metabolized in downstream active steroids such as testosterone, progesterone, estrogen, so you can only imagine the potential side effects here. Third, it has very poor oral bioavailability. This is the antithesis of a new molecule that you can develop for this indication. What do we do? This is where the team made a big difference. Aelis Farma actually created and discovered a synthetic compound that will bind on that allosteric site on the CB1 receptor, and that is AEF-0117. Let me give you a little bit more information about this compound and why we actually started to be quite excited about it. Why did we get excited? For several reasons. First of all, very clean phase 1 trial. Single ascending dose, multiple ascending dose. Very good toxicological profile as well. This phase 2A study run by Dr. Meg Haney at Columbia University. Where she actually demonstrated that the compound, first of all, decreases the cannabis subjective effects. You can see here a few examples where you observe a very nice dose-dependent decrease in these subjective effects. Dr. Haney also demonstrated that this compound significantly reduces cannabis self-administration. Altogether, this was an indication to us that there was a pathway forward. Where are we today? We took an option on this compound, now we have an opportunity to potentially exercise our option upon positive results from what we call a phase 2B or clinical proof of concept. You can see that this is a pretty big clinical proof of concept with 330 patients. We are going to assess to what extent the compound can actually significantly inducing a greater proportion of subject with a response of less or equal than once a week use of cannabis. That's pretty stringent. Most of these subjects are suffering from moderate to severe cannabis use disorder and use, you know, five or more times per week. Timelines, we're estimating the last subject, last visit in that trial in the first quarter of 2024, and a final clinical study report in the third quarter of 2024. Let me now talk a little bit about INDV-2000 as a non-opioid medication for opioid use disorder, and why is that important? You have heard today that the great majority of patients will probably have to stay in treatment for many years. Some patients do not want to stay in treatment on an opioid-based medication. For all those who do not wish to stay on an opioid-based medication, we want to offer a non-opioid medication option. This is what we are trying to achieve with INDV-2000. Let me talk to you a little bit about the mechanism of action. INDV-2000 is what we call a selective orexin one receptor antagonist. In the brain, you basically have two main orexin receptors, the orexin one and the orexin 2. We are not really interested in the orexin 2. Why is that? Because that receptor is mainly localized in brain regions that are involved in arousal and wakefulness. Actually, there are some medications right now that have been approved by regulatory agencies that are what we call DORAs, dual orexin antagonists, and they are used actually for sleep disorders. There is compelling evidence in addiction science that the orexin 1 receptor is really the one that is localized in brain circuits that are heavily involved in reward, including drug reward. There is clear evidence from the non-clinical literature that you could make a difference if you were to develop a selective orexin 1 receptor antagonist, and this is exactly what we have done with INDV-2000 in partnership with C4X Discovery. Where are we? A little bit back in time in 2019, we actually received a $10.6 million grant from the NIH, through the NIH HEAL Initiative, to really enable us to start the non-clinical and clinical development of this compound. That was very good news for us to receive that grant from the NIH. Very nice recognition. In 2021, we mostly dedicated our time to focus on the phase I single ascending dose of this product. We actually tested eight doses, characterized the full pharmacokinetic profile, the toxicology profile, and the safety profile. The profile looks really good so far. This year and next year, we will move to the second part of the phase 1 trial, really dedicated to what we call a multiple ascending dose. We are also going to perform additional clinical studies and, very importantly, additional non-clinical toxicology studies. That is the plan with this product. The last one I would like to share with you is INDV-1000 for alcohol use disorder in partnership with Addex Therapeutics. This is actually a GABA B positive allosteric modulator. You may ask me, "Can you please repeat this?" because it's a little bit complicated, so I will try to make it as easy as possible. First, let me give you a little bit of background. Why the GABA B receptor? Prototypical GABA B agonist is baclofen. Baclofen is a very old drug that was originally approved in the early 80s for spasticity. I seem to remember that the first paper, one of the first papers in the literature about using baclofen for substance use disorder was in around 1985. Actually, it was a paper on cocaine. Over the years, people really started looking at the potential for a GABA B agonist, such as baclofen, in a broad range of substance use disorder, including alcohol. This book in the year 2000. It was between around 2005 from Dr. Olivier Ameisen. Olivier Ameisen was a very successful French physician who unfortunately suffered from alcohol use disorder. Reading the literature, he discovered baclofen and decided to self-treat with baclofen. The book is all about his journey through alcohol use disorder, but also his own treatment with baclofen. In his case, the treatment was very successful. It has been a major patient-driven effort in France under the leadership of Dr. Mazan as well. Again, things are always more complicated than we think. There are, unfortunately, a lot of limitations of baclofen for this particular therapeutic indication. Here are a few examples. Number one, because of its pharmacokinetics, you need to use the drug at least three times per day, which for an indication like alcohol use disorder, let's be honest, it's already a no-go. It's extremely difficult to keep patients in treatment retention if you have to take at least three times a day. There is a very careful dose escalation to prevent some of the side effects early on in treatment. Unfortunately, for alcohol use disorder, you probably need to go far beyond the currently approved doses of 80 milligrams per day. There is a potential for side effects, especially sedations. There have been multiple attempts to actually create new formulations, all these attempts have failed. It was approved in France, a very restricted approval. Unfortunately, what we have seen also with a broader range of off-label use of the drug is an increase in reports of mortality. Again, there is always a solution. What is the solution in this case? A GABA B positive allosteric modulator. A little bit similar to what I explained for AEF-0117. The GABA B receptor has another allosteric modulator site. The idea is, in order to keep the clinical efficacy that we see but significantly improve the safety profile, is to develop an allosteric modulator at that allosteric site. Now, this is complicated. We had to go back to the drawing table, so to speak, of what we call a lead identification and then lead optimization program. There are typically three main components of this major medicinal chemistry efforts. You characterize your new lead molecules into biology, both in vitro and in vivo. Last but not least, you start characterizing the drug metabolism and the pharmacokinetics. We currently have a few lead compounds, and we are aiming at selecting one of these lead molecules for candidate selection in the first quarter of next year. Last section of the presentation is to talk briefly about the future. To us, it is really critical to develop over many years now a very deep understanding of the brain circuits that play a key role in substance use disorder. Very importantly, then the next step is to try to identify key receptors within these circuits. To keep things relatively simple, there are currently three main brain circuits that play a key role in substance use disorder in general. The first one that you can see there in blue is what we call the basal ganglia. This is a series of circuits that are heavily involved in what we call incentive salience. What is incentive salience? It is the increased motivation to seek a drug, and that motivation is actually triggered by environmental cues that have been previously associated with drug-taking behavior. For example, if you used to take the drug with very specific people or in a very specific place, even if you are abstinent, but you meet some of these people out of chance or you just walk by that place, just that cue might be enough to trigger relapse or reinstatement of drug-seeking and drug-taking behavior. That is the power of what we call these conditioned cues, and that is a core problem in substance use disorder in general. That circuit is also, unfortunately, involved in pathological habits and perseveration. Even if you know that there will be very negative consequences by seeking the drug and taking the drug, you feel compelled to go for the drug, seek the drug, and take the drug. This is related to major dysfunctions in that brain circuit, the basal ganglia. Second big circuit is the extended amygdala. This is a series of networks that are involved in the negative emotional state that you may feel under drug withdrawal. When the drug is no longer there, this activates this extended amygdala system. Then the last one, and certainly not the least, because it plays a critical role, is what we call the prefrontal cortex. That brain circuit is really driving the executive function and the decision-making. Again, it's this very complex interaction between pathological habits and persevering in that habit. You know that the consequences are negative, you still make the decision to go for the drug. That's the prefrontal cortex, alterations in that prefrontal cortex circuit. Last but not least, this is also a circuit that drives craving for the drug. Needless to say, you understand the complexity of the task at hand. You know, over many decades now, we improved our understanding of some of these major alterations in some of these circuits. For us, as a company, the goal is to really try to understand what are these key receptors, what are, for example, the receptors that are present in nodes interacting with these three systems. The next step, once we have identified these key receptor systems, is to assess whether or not there is a molecular target that actually fits that receptor system. Last but not least, we do a lot of due diligence. That's the business development part of the deal, whereby we look for potential partners who may have already developed a drug that is targeting these key receptor systems. On that note, I thank you very much for your attention, and it's my pleasure to introduce you to my colleague, Nina DeLorenzo, because how we deliver really matters. Thanks, Christian. Good morning, everyone. My name is Nina DiLorenzo, I'm our Chief Global Impact Officer. You've heard this morning about our exciting plans to deliver growth in the coming years, how we deliver this growth really matters to us. As Mark noted earlier, we believe our long-term success is directly linked to operating responsibly and in a way that both minimizes our impact on the environment and maximizes our positive social impact. Today, I'm gonna introduce you to Indivior's ESG and sustainability strategy. I'm gonna talk about our activities and outline some of our early progress. We're a relatively young company, we're at the beginning of our ESG journey, it's a top priority. It has the attention and ownership of the board, management has been charged with operationalizing it. We are building it into everything we do. We've worked in the past few years to formalize our internal structure around ESG, and now we're looking ahead to expanding our efforts. Our ESG framework links directly to our vision as a company. We used a patient lens to frame our strategy to maximize Indivior's positive global impact and shareholder value through our mission of making innovative treatments for substance use disorders and serious mental illnesses and to change lives for the better. The pillars of our strategy are to transform patient lives, prioritize our people, conduct our business with integrity, meet our environmental responsibilities, and provide our products. Importantly, these pillars are aligned with several of the UN's Sustainable Development Goals. We've also aligned our work to other leading disclosure frameworks. Our strategy is to reduce our environmental impact in line with good practice, lead on social impact, and establish Indivior as a company committed to an effective, sustainable global integrity and compliance program. This isn't working. I'm having issues. There we go. On the environment. We recognize the importance of climate change, and we support the activities of groups such as the Intergovernmental Panel on Climate Change and the UN Framework Convention on Climate Change, as well as the various initiatives that aim to achieve greater transparency and to enable stakeholders to monitor the related areas of climate change and environmental performance. In 2021, we established the foundations of our approach. Specifically, we enhanced our scope 1 emmision and scope 2 emissions reporting and began to explore appropriate reduction targets. For 2022, we enhanced our reporting of activities related to climate change as our strategy is maturing and developing. We will begin target setting once we have fully established our baseline. We also look forward to minimizing our emissions by installing solar panels and a geothermal heat pump at our Hull, U.K., facility and exploring a more sustainable fleet for our U.S. sales team to include switching it over to hybrids in the near future. We're pleased to say that earlier this year, as Mark mentioned, we became a member of the UN Global Compact. On the social aspects, at Indivior, we see our social purpose as a major strength. We seek to make this an area of leadership for the company. In addition to the inherent positive social impact of the products we provide and the patients we help, we're setting out to develop a comprehensive impact strategy that amplifies our work supporting underserved and stigmatized patients. A strategy that creates shared value for our business and for our stakeholders, something that can help transform the disease space. We're excited about the possibilities ahead. Earlier this year, we were pleased to be certified as a great place to work with an 88% employee approval rating. We value our engaged culture at Indivior and believe it's a key advantage for us as we drive our business strategy. On social issues, we seek to bolster training and engagement on diversity and inclusion. Indivior benefits from having a diverse set of perspectives. We know it helps us grow our business and meet our commitments. On governance. We know that we have a special responsibility to the patients we serve, to conduct ourselves with a high level of integrity, as well as to investors to ensure they have confidence in our company. Our commitment to excellence in meeting our government agreements is a testament to Indivior's strong culture and engagement, and we have worked to put in place an effective and sustainable global integrity and compliance program. This aspect of our business remains a significant management priority. Additionally, on governance, board diversity continues to be an important area of focus. Since 2021, there have been five new appointments to the board, three of whom are female. While we've made significant strides, we recognize there's more to be done to advance diversity and inclusion at Indivior. Finally, on governance, we plan to incorporate ESG metrics into management compensation in the near future. As you can see, we are actively developing our initiatives in line with industry best practice. You'll see this outlined in our inaugural sustainability report, which I'm very happy to say will be released in the coming weeks. Some of the information contained in it can be found in our annual reports over the years, but we felt it was important to highlight the key E, S, and G information in a distinct publication to make it easier for investors to access. We hope you'll take a look at it when it's published. It will be housed on our Indivior website. Thank you for your time, and I'm pleased to hand it over to Ryan Preblick, our CFO. Thanks, Nina, and good morning to everyone. I'm Ryan Preblick, the CFO. I've been with the company now for 10 years. It's a pleasure to be here today to share more details on our medium-term financial outlook and our capital allocation priorities. In my session, I wanna leave you with four key takeaways. First, we have an attractive growth profile based on our currently marketed portfolio, and we expect to add to this over the longer term with our pipeline and potentially through business development. As Mark noted, our growth projections today do not include the Opiant acquisition since it is not closed yet. The key is, of course, SUBLOCADE, on which we now expect to deliver a peak net revenue of over $1.5 billion. Second, we have a scalable business model with a unique commercial platform. We will leverage this model both through traditional field sales and, more importantly, our dedicated efforts across organized health systems, and that includes the criminal justice system as well. This will be supported by patient-focused systems, including our hub and by a GNA platform that provides value-added support services, including the continuous upgrade of our compliance capabilities. Third, the strategic priorities Mark spoke to. Growing SUBLOCADE, diversifying our business, progressing our pipeline, delivering operational excellence are all well-funded through our growing EBITDA and healthy cash balance. Our balance sheet gives us significant flexibility to invest in growth, to meet our obligations, and to generate shareholder value. Lastly, we expect to generate strengthened free cash flow in the coming years, which we will deploy according to our capital allocation priorities. Consistent with our strategic priorities, this framework is focused on reinvesting in our growth drivers, de-risking the business, including through diversification and potential business development, and returning excess cash to shareholders. Let me start with our growth profile. Since 2020, we have delivered double-digit net revenue growth, powered primarily by SUBLOCADE. Our adjusted operating profits have more than doubled. Over that period, based on strong commercial execution, SUBLOCADE has become our biggest product by net revenue, and we are now starting to see PERSERIS make a meaningful contribution as well. In fact, our full year guidance of $405 million-$420 million puts SUBLOCADE on track to become the number-one selling global brand for opioid use disorder in 2022. As you heard today, we are confident we can deliver peak net revenue of more than $1.5 billion. For PERSERIS, as Glen explained, we remain committed and confident in delivering its potential peak net revenue in the range of $200 million-$300 million. Having touched on net revenue, let me now discuss margins. We are confident that we can generate margin expansion in the coming years based on our scalable business model. This slide shows our path forward by expense category. Over 2021 and 2022, we have made significant structural growth investments to support SUBLOCADE in organized health systems and to expand the national sales coverage for PERSERIS. Going forward, we will continue to fuel the commercial business in a tactical fashion when appropriate. As a consequence, you should expect to see our sales and marketing spend grow at a more modest pace versus the last two years. R&D, on the other hand, is expected to increase as a percent of net revenue as we move closer to benchmarks in our industry. This will reflect our strategic focus on building a strong and balanced pipeline. In addition, we will conduct the necessary life cycle management studies to support our long-term ambitions for SUBLOCADE. Generating the real-world evidence for SUBLOCADE is a critical part of the value proposition for our commercial teams, especially as we drive deeper penetration into the OHS. Lastly, on G&A spend, we underwent a significant cost reduction program in 2020. Going forward, we plan on maintaining a disciplined and efficient approach in this category. Taken together, these three vectors plus improved gross margin can support sustained margin expansion. I now want to touch on how we will reinvest our profits for growth, meet our obligations, and return value to shareholders. Over the period since 2020, consistent with our adjusted operating profits, we have more than doubled our EBITDA, even with the step-up in growth investments we made the past year. This, in turn, has helped us to grow our gross cash and investments position to more than $1 billion. This position of balance sheet strength, when set against the context of our relatively constrained capital expenditure requirements, gives us tremendous flexibility. It means we can fund our strategic priorities while at the same time meeting our obligations. It also means we can pursue organic and inorganic growth opportunities to strengthen our leadership position in addiction treatment and science. Lastly, it gives us the opportunity to return excess cash to shareholders, as evidenced by our 2 $100 million share buyback programs. This slide sets out our capital allocation priorities in detail. As I mentioned, we expect to maintain the financial flexibility to prioritize growth and shareholder returns while also meeting our obligations and de-risking the business. We will also place a great emphasis on operating in a responsible and sustainable manner. Our growth investments will be focused on commercial execution, patient access, and progressing our pipeline. We will also seek business development opportunities as supported by our Opiant announcement that will extend our global leadership position in addiction treatment. Lastly, we will seek to return excess cash to shareholders when appropriate. We believe this balanced approach to capital allocation will drive substantial shareholder value in the short, medium, and long term and help us deliver our vision and mission. As Mark touched on earlier, here is more detail on our medium-term profitable growth framework. As already noted, this is built on our current business only. Based on the outstanding prospects for SUBLOCADE and PERSERIS, we expect to deliver double-digit compounded net revenue growth over the medium term. Let me walk you through some of the considered assumptions. First, we expect underlying Vmac growth to be in the mid to high single digits. We assumed a new entry into the LAI market here in the U.S. Third, we assume SUBOXONE film share will ultimately trend towards analogs with a fourth generic coming into the market soon. Although the timing on this is unclear, and we remind you that we do not promote the product in the U.S. Lastly, I want to specifically call out that we expect SUBLOCADE to meet our previous $1 billion net revenue target in terms of run rate by the end of 2025. Now, we expect to generate positive operating leverage, as I discussed earlier. Within this, we expect the improving product mix to lift our gross margin to the mid-80% range despite the current backdrop of inflationary pressures. We will focus our growth investments on U.S. commercial and R&D as we scale our business model. Lastly, we expect to generate strengthened free cash flow. Our CapEx needs are relatively modest despite our ongoing investment in additional manufacturing capacity and IT. Our strong free cash flow will allow us to take the balanced approach to capital allocation I set out earlier, focused on delivering sustainable growth and shareholder returns. Next, I want to update you on our plans for a additional listing here in the U.S. As a reminder, we received strong shareholder support at our EGM in September. The news today is that we have chosen Nasdaq to be our trading venue with a target listing of our shares in the spring of 2023. We have a lot of work to do before then to ensure that we meet SEC financial reporting and Sarbanes-Oxley requirements, this is well underway, and we are confident we will deliver this important initiative to elevate Indivior's profile in its largest market and attract a broader group of biopharma-focused investors. In summary, I would like to thank you for your attention and remind you of the four key takeaways that I started with. We have an attractive growth profile and a scalable business model, which are reflected in our medium-term outlook. Our strategic priorities are well-funded through our strong balance sheet, and we will deploy our strength and free cash flow in the coming years to deliver sustainable growth and shareholder returns. With that, I'll hand it back to Mark for closing comments. Thank you. Just a few comments before we get to Q&A. I hope you came away today just seeing the passion that the leadership team brings to both the disease space as well as the ownership. It certainly is representative of the 900 plus employees that we have at Indivior across the 39 countries we operate in. I also hope that you've come across with the same confidence that we have in the future for Indivior. We have a strong growth profile in the years ahead. We will deliver sustainable shareholder value in the years to come, all based on the following four factors. We are the global leaders in addiction. We take the unique, passionate insights that we have from both the patients and the disease space and merge those with breakthrough science to create great treatments. Second, SUBLOCADE is a transformational asset for the treatment of moderate to severe opioid use disorder and will deliver in excess of $1.5 billion of net revenue. Third, we continue to seek diversification opportunities in both addiction and comorbidities, both organically and through business development. Lastly, we will generate significant cash flow through continued operational excellence moving forward and to support delivery on our strategic priorities. With that, we'll go ahead and transition to Q&A section across the entire presentation. If there's more questions on SUBLOCADE, we can go to those, but we can also have some on the operating model. I'll invite the management team to join me up here and hopefully grab a mic. Thanks, guys. My name is Isaac. I'm with Piper Sandler. On PERSERIS, can you give us some details on how many reps you have in the field, targeting physicians and how large the call audience is? Secondly, can you share with us, I guess your thoughts on... I mean, I think we know that the category is growing, the LAI category is growing, but can you share with us your thoughts on kind of why the category isn't growing faster? Is it on the patient side? Is it on the payer prescriber side? Lastly, on PERSERIS, can you talk about your thoughts on peak sales in the context of a potential new entrant in the LAI risperidone category next year? I know Teva has their FDA action date scheduled sometime for the first half of 2023, and that's an LAI risperidone product, but also a ready-to-use product and a subQ, of course. That'd be helpful. Thanks. Thanks for that, Isaac. I think I'll take the last question, then I'll hand to Glenn, you know, with regards to our call platform and the number of reps we have out there. Listen, I think what we've seen is every time a new entrant has come in here, it's accelerated growth in the category. You spoke to, you know, the penetration targets with regards to the market, and that is still only at 18%-20% penetration. There's plenty of room for growth with multiple opportunities there. We see significant differentiation existing with PERSERIS that will continue to enable us to hit that $200 million-$300 million of peak revenue moving forward. Glenn, would you like to address, you know, what our platform is and what our call platform is like? Yes, sure. Sure. Yes. Thanks for the question. We have 110 sales reps, clinical specialists and institutional specialists. It's a mix of folks that call specifically on institutions and those that call on HCPs primarily. In addition, I would just like to say that we leverage all of the other ecosystem partners in the space that exists for both brands. That brings in a whole host of other people that are involved in the process. The call platform, the question about call platform size, I think we're looking at the universe of HCPs. In the long-acting injectable space, there's about 8,000 HCPs that make up 80% of all the prescriptions. We call on the vast majority of those. We, we do have a segmentation profile, though, that we think makes of clinicians that are more likely to prescribe PERSERIS based upon what we've seen in terms of the uptake already. We focus the call platform on ensuring that we're covering those with the right level of reach and frequency. Was there another- I think that's it. I think that's it. Thanks, Glen. Thanks, Isaac. Please. Hello? Oh, there we go. Hi, it's Jason Jeffries. A couple of questions maybe for Christian, I guess. Just kind of curious if we're looking over the mid to long term for Indivior. We've obviously seen the move from SUBLOCADE to SUBOXONE to kind of SUBLOCADE. Some years ago, there was a swallowable tablet in development, which wasn't. Have we reached the end of the runway, would you say, in terms of i nnovation with that compound. Now it's more about are there is an addiction or is it something even kind of perhaps early stage, you can't go into detail at the moment, but we could maybe see another formulation. My second question is just in terms of some of the other studies with Sublocade. I'm just kind of curious what the opportunity is on the pricing side to demonstrate the value benefits. There's perhaps lower hospitalizations, that introduces other kind of savings into the system or in the criminal justice system, sort of studies to show, if you're with the patient once a month versus once a day, what the other kind of savings are. Does that give you essentially potential pricing power which may not be embedded into expectations at the moment, but could be a value consideration to the company? Thank you. Thanks for those, Jason. Yeah, we'll start with Christian, and then if needed, we'll ask Vishal on the criminal justice side to add his thoughts on those studies. Yes. On, on the formulation side, obviously we are developing a lot of studies, as you have seen, to focus on SUBLOCADE right now because we really believe that this is the treatment of choice for opioid use disorder. That's really our top priority. Of course, we are very open to additional possibilities in terms of formulations, mainly on the long-term maintenance side. That, that is definitely a possibility. I will not answer the pricing part, but I could not take you through all the studies that we currently are running. There are several studies that are specifically looking at the cost effectiveness of SUBLOCADE versus standard of care in a broad range of treatment settings. As in the criminal justice system, the Veterans Health Administration, but also in the emergency department. Yeah. I think the key on that, Jason, is those studies are being done in those sub-channels across the organized health system. You've got the IDNs, you've got the government accounts, you know, as well as the criminal justice system. Anything else to add on that, Vishal, with regards to- Yeah, just to add on your second question. Thanks for the question. Building on Christian's point, I think the studies are really focused on all the relevant drivers. I think as I presented earlier on, our focus remains in growing the base and the growth opportunity really sits in access to patients for the medication and more number of patients on treatment profiles. That remains the focus and all the studies help educate the system why this is a good investment to making patients. Thank you. Thank you. Get one right down here. Cheers. Max. Hi, it's Max Herrmann here from Stifel. Just a few questions on PERSERIS and then on your sort of margin, longer term margin guidance. Just on PERSERIS, I mean, you gave some great data demonstrating, I think, people, doctors who are prescribing, PERSERIS at the moment. I think you said that their share of new scripts was 6%, so that's obviously a significant amount of prescribing is going elsewhere to other LAIs. They're obviously familiar with PERSERIS. Is that share of voice that is the issue here or what is driving, you know, doctors to prescribe other LAIs in reference to PERSERIS? Be interested to know in terms of payer coverage. You obviously talked about that being great for SUBLOCADE. Just wonder where you are now with PERSERIS for coverage. Those are the two questions on PERSERIS. Then just in terms of margin evolution, maybe for Ryan, obviously you talked about moving to industry trends for R&D spend. That sort of is different between depending on maybe when you're a specialty pharma company or whether you're a kind of a general pharma company. Obviously, you guys are more in the specialty market. I just wondered, are you talking about up to sort of 10% range when you talk about the peers, or are you talking about more like mid-teen range where other pharma companies target? Then on the gross margin side, clearly historically, you know, pre-generics coming in for SUBOXONE, your gross margins were more closer to the 90%. Mid 80s% seems to be low, particularly given comments previously that SUBLOCADE was a higher margin product. Just wanted to understand what's driving that. There's the questions. Thanks for those questions, Max. Yeah. Maybe I'll start with just the reminder that we're still in the first year of a full-scale launch on PERSERIS. We only went to the national launch starting in January. That traction that you're seeing coming out of COVID and really getting that full national launch is starting to drive the growth you're seeing. Glen, you wanna just talk about some of the headwinds that you see out there but the opportunities moving forward? Yeah, that's a great question. I think, yeah, there's a share voice issue. There's a heck of a lot of other LAIIs out there. Part of the whole point in going to the larger team was to address the share voice issue and make sure that we're covering a much wider range of practicing clinicians. Coming out of COVID, I think that was certainly an issue. It's hard to drive penetration with a challenger brand when you can't see anybody. I think that's been a challenge that we're now starting to see abate as we have expanded the team and the COVID restrictions are reducing. That's fair. The question on coverage is great. The coverage on PERSERIS is. Our objective there is parity with the rest of the category, and we've achieved that. We feel very confident in the coverage. There are, you know, a couple of areas that we continue to optimize. Generally speaking, you know, it's excellent coverage for PERSERIS. Thanks, Glen. Thanks, Max. Ryan, do you wanna talk about, you know, the R&D spend as well as the gross margin profile? Thanks, Mark. On the R&D spend, right now we're at 7%. Certainly took a step up this year, and that's one of the reasons why we called it out as we try to progress more in this goal of ours to have a strong and balanced pipeline. That's one of the reasons why we spent some time this year trying to explain to all the new products that Krish and team is working on. We are gonna continue that ramp as we spoke about, because one of the major key priorities is to have a strong balanced pipeline for the long term. When we say double digits, we're looking at low double digits here. That's what the benchmarks would put us at in our current industry. The exact quantum of that could differ based upon the mix of projects that he's working on and also where they are in their time cycle. That would be on the R&D. In regards to gross margin, the range that we put out there today is one that we have confidence in regards to what we're looking at. Also keeping in mind that we are dealing with some inflation that we're trying to factor in as well. You are right. With SUBLOCADE at the top of that pyramid certainly does have a nice margin profile. We do have to consider that PERSERIS will be growing, Throm will still have some residual, as we talked about today, the balance of the rest of the world business is doing okay, but that part of the portfolio does not have the high gross margin mix that we have on SUBLOCADE. When we try to factor in mix of the business, seeing some of the headwinds, what we're dealing with inflation, that range was what we felt most comfortable putting out at this point. I just maybe follow up on the first question. What is the share of voice that you have relative to the? We do have some market research on that. Just recently, we think we're at about 11% or 12%. Growing. It's about doubled since last year. In terms of insurance coverage. The insurance coverage? Yeah. Oh, yeah. I answered that question. Yeah. It's excellent. We're at parity with the category. Yeah. What does that mean? That means that... I mean, what percentage? Is it 70% coverage? Oh, no, 88%-89%. Yeah. Eighty-nine. Yeah, yeah. On the point on insurance coverage in this category, just so that you're aware, you know, this is highly disabled group of folks, and the coverage really aligns, you know, with ensuring that there aren't a lot of barriers to those folks getting the medicine. You know, while there are some small plans that have issues at the end of the day, we feel very comfortable. The HCPs that treat in the space understand any of the barriers that they have to overcome in terms of prior authorizations and so forth. Thanks, Glen. Thanks, Max. I'm sensing people are hungry and wanting food 'cause there's not very many questions. Any other questions before we close? All right. Oh. Oh, we got one? Oh, sorry, I didn't see it. Sorry. Just quickly, in terms of you mentioned that no, currently any generic, versus long-acting in this antipsychotics. What are some of the expectations sort of in the market if you look sort of consensus estimates and where some of the. Anything in the near term in terms of generic competition to some of those existing brands? Go ahead, Glen. Yeah. Yeah. You know, we've seen there's been some, you know, cases that have, that have come forward in the past, I don't know, two years on some of the large products, and they've unsuccessfully been able to achieve that. In the near term, we don't see anything meaning, you know, certainly not in the next 18 months or so. We don't see anything that would be coming into genericize the market. Unless, I think, just to be clear, it is hard to create generics of long-acting injectables. It's challenging. Not that that gives you any, you know, greater sense of protection, but at the end of the day, I think it's just challenging there. The ones that have come in the past, I don't know, 18 months or so have been unsuccessful. Thank you, though. Don't have absolute certainty for you, but hopefully that answers your question. One last call for questions. All right. Let me thank you for the significant investment you've made in Indivior this morning. We really appreciate it. We'll look forward to a bit of time, over lunch, of course, continued one-to-ones and conference time together. Thank you very much.